# Image Risk Assessment of the Thyroid Cancer Model Based on Discriminant Analysis and the Value of TAP and CEA Combined Detection

Authors: Bin Wang; Shengliang Wang; Shaolei Lang; Li Liang; Yang Yang; Yan Xue; Yinxia Xu
Journal: Journal of Healthcare Engineering
 (2021)

---

## Abstract

The incidence rate of thyroid disease is increasing rapidly worldwide, and the number of thyroid patients is increasing. In this study, serum TAP (tumor abnormal protein) and CEA (carcinoembryonic antigen) were used to detect patients with thyroid nodules of class IV and above to explore the value of serum TAP combined detection of CEA in the risk assessment of thyroid cancer. In this paper, 400 patients with thyroid nodules above class IV diagnosed by physical examination in our hospital health management center from January 2019 to June 2021 were included in the study. Combined with the pathological test results, the patients were divided into risk groups. At the same time, different groups of serum TAP and CEA levels were detected by aggregation and electrochemiluminescence methods, and serum TAP and CEA levels were analyzed according to the pathological diagnostic indicators of CEA levels. The results showed that the levels of serum TAP and CEA in patients with thyroid cancer were significantly higher than those in patients with benign thyroid diseases, and the difference was statistically significant (P < 0.05). The sensitivity, specificity, and AUC under the ROC curve area of serum TAP were 85.25%, 85.06%, and 0.605, respectively. The sensitivity, specificity, and AUC under the ROC curve area of serum CEA were 89.85%, 88.00%, and 0.627, respectively. The sensitivity, specificity, and AUC under the ROC curve area of serum TAP combined with CEA were 96.84%, 96.79%, and 0.915, respectively. Therefore, the combined detection of serum TAP and CEA has a high early screening value in thyroid cancer.


---

## Body

## 1. Introduction

At present, the detection rate of thyroid cancer is still low, and many methods cannot balance the sensitivity and specificity threshold, leading to that many patients cannot be diagnosed until they are seriously ill. At present, CEA and TAP are commonly used in the field of tumor detection, but their detection rate is generally 60%–70%. Given the results of blood glucose detection by some scholars, this paper proposes a diagnostic method of thyroid cancer detection by CEA combined with TAP.Many scholars have analyzed the effect of the CEA content on patients. For example, Pistollato et al. believed that early thyroid cancer may have a potential protective effect on thyroid cancer. This effect seems to last as long as six years after the diagnosis of thyroid cancer. The mechanism may be that metformin, an antithyroid cancer drug, can inhibit cell cycle progression and induce apoptosis. This leads to the antimitotic effect and reduces the growth-stimulating effect of insulin [1]. Detweiler et al.’s study found that the incidence rate of thyroid cancer increased by 20% compared with patients with low CEA content, and the risk was mainly in women. There was no significant difference in men, and the effect was also related to age and found only in 60 years of age in the population. The mechanism may be due to different levels of serum insulin in patients with thyroid cancer [2]. Kuo et al.’s study found that patients with high CEA levels had an increased risk of thyroid cancer compared with those without high CEA levels. The reason may be related to hyperglycemia, hyperinsulinemia, and insulin resistance. These factors lead to a significant increase in IGF-1 levels. Insulin itself can directly induce tumor growth [3]. Mohammadi et al. found that thyroid cancer incidence rate was positively correlated with thyroid disease in women, but no relationship was found in [4] among men. Xia et al.’s study showed that upregulation of TAP enhanced the migration, invasion, and channel-like structure formation of hepatoma cells and promoted the transformation of the epithelial-mesenchymal process and the expression of stem cell-related protein TAP [5].In terms of hormones, Cesareo et al. found that TAP can downregulate SOX2 by mediating Smad1/5/9 phosphorylation and Smad4 expression, thus inhibiting the growth of cultured cells of multiple groups of glioblastoma [6]. Mian et al. found that the high expression of TAP may activate the Akt/mTOR pathway, promote the formation of microcalcifications in breast cancer, and then produce resistance to targeted or endocrine therapy, indicating poor prognosis [7]. Panebianco et al.’s experiment showed that the high expression of TAP7 in thymic epithelioma was closely related to poor prognosis, which may become a new prognostic biomarker of thymic epithelioma [8]. Liu et al.’s study suggested that MTAP (microtumor abnormal protein) can enhance the survival and drug resistance of renal clear cell carcinoma by promoting Nrf2 phosphorylation and activating TRIM24 [9]. Witt screened and confirmed that several genes including the CEA gene were involved in the pathogenesis of thyroid cancer [10]. The above studies explored genes and common clinical tests, especially the correlation of serum indexes. However, the detection rate of thyroid cancer is still low, so this paper uses TAP and CEA combined detection to predict the risk of thyroid cancer in patients with thyroid nodules of class IV and above and analyzes its value.In this study, serum TAP and CEA detection indicators were used to detect patients with thyroid nodules of class IV and above and to explore the value of serum TAP combined detection of CEA in the risk assessment of thyroid cancer. In this paper, patients were divided into risk groups according to the results of pathological examination, and serum TAP and CEA levels in different groups were detected and compared by agglutination and electrochemiluminescence. At the same time, the diagnostic indexes of serum TAP and CEA levels were analyzed based on the pathological results to analyze the value of these two indicators in the diagnosis of thyroid cancer.


## 2. Detection Index and Evaluation Method

### 2.1. Thyroid Cancer Detection Index

Thyroid cancer accounts for about 3.8% of the world’s cancer-related diseases, with a latent period of 5–10 years and no symptoms. Most of them can be cured, especially the prognosis of the thyroid is the best, but early lymph node metastasis and tumor invasion often occur. Although the cure rate and mortality rate of patients are decreasing, the incidence rate is still increasing [11]. Therefore, it is necessary to explore the early detection, clinical analysis, and prognostic indicators of thyroid cancer [12]. A large number of studies have shown that TRPC5, as a Ca2+ channel, participates in the occurrence of many malignant tumors, which mainly mediates Ca2+ imbalance by triggering the Ca2+ entry pathway or changing membrane polarization, thus promoting the occurrence of malignant tumors [13]. Chemical resistance is the main feature of a malignant tumor. TRPC5 with abnormally high expression in breast cancer promotes the activity of the Ca2+ channel, and the Ca2+ signal activates transcription factor NFATC3 to start the transcription of P-glycoprotein, resulting in chemical resistance [14]. In colon cancer, TRPC5 activates the TAP signaling pathway by promoting hypoxia- inducible factor-1α expression to induce epithelial-mesenchymal transition and promote tumor metastasis [15]. TAP may hurt the clinicopathological characteristics of the thyroid and may lead to a worse prognosis [16].Abnormal glycosylated protein (TAP) is a sensitive indicator to evaluate the metastasis or recurrence of thyroid cancer, which plays an indispensable role in the early screening, treatment, and prognosis of patients with thyroid cancer. However, to a certain extent, some factors may interfere with the TAP level in patients, resulting in the false positive or false negative in clinical detection [17]. On the contrary, for thyroid cancer patients with relatively late diagnosis, the serum carcinoembryonic antigen (CEA) level will increase in varying degrees, while the TAP level will be at a low level [18]. To explore the value of serum TAP combined with CEA in risk assessment and early screening of thyroid cancer, the serum TAP and CEA levels and diagnostic indexes of different groups were detected and compared by the electrochemiluminescence method [19]. In addition, overexpression of TAP can also effectively improve the activity of vasculogenic mimicry-related proteins and ultimately enhance the vascular invasion of hepatocellular carcinoma [20]. TAP family is widely involved in the development of tumors. However, up to now, there are few reports on the relationship between the TAP family and thyroid cancer [21]. MTAP is an important member of the TAP family. According to the data of the NCBI (National Center for Biotechnology Information), the expression of MTAP in normal thyroid tissue is significantly higher than that in other organs and tissues [22]. Patients with Graves’ disease have a higher risk of thyroid disease, and the thyroid in patients with Graves’ disease shows a higher ability of invasion and metastasis [23]. This suggests that there is a certain correlation between MTAP and thyroid [24]. This study first revealed the correlation between MTAP and thyroid through bioinformatics mining and analysis [25]. To further verify the conclusion, real-time PCR and western blotting were used to detect the expression of MTAP. The expression of MTAP in thyroid tissue was significantly lower than that in adjacent tissues, and the expression of MTAP in claim-bearing thyroid tissue was also significantly lower than that in thyroid tissue without claim. Based on this, we preliminarily infer that MTAP may be a tumor suppressor gene of the thyroid. The expression of MTAP in thyroid tissues was significantly lower than that in adjacent tissues, and the expression of MTAP was related to cervical lymph node metastasis. This suggests that the upregulation of MTAP expression may inhibit the proliferation of thyroid cells and lymph node metastasis. MTAP is expected to become a new biological target and provide a new direction for the diagnosis, treatment, and prevention of thyroid recurrence.


### 2.2. Diagnostic Index Analysis Algorithm

In the problem of the serum evaluation index, people often want to reduce the classification errors as much as possible. Based on this goal, we can measure the performance of the classification algorithm. Suppose there areC categories in the classification problem, and the states of each category are expressed as i1,...,ic; PiandPx are prior probabilities, a class-conditional probability density function of the occurrence of class I is represented, Dx represents the d-dimensional feature vector, and the goal of classification is to predict the category of serum indicators based on this feature vector. The so-called error rate refers to the average error rate.(1)DxgainY=Px−avgσY′,σicσY,Pxwkt=ω1dkc+ω2dkc+ω3TkNcK+ω1PKcK.There are two types of classification:(2)Dκ=2kk+1+12+12kc2−c132+2c2−c13.If the feature space is divided into two types by the discriminant function, they are as follows:(3)Pxi,wj=PdiPwj|di;Pwj|di=∑k=1KPwj|zkPzk|di.Among them,R1andR2 are divided into two regions. Correspondingly, for the multiclass classification problem, if we divide the feature space into C regions, the average error rate based on these C regions is E:(4)ER1,R2=log2PR1&R2PR1PR2.It can be seen from equation (4) that the calculation of error rate depends on the distribution of data (including prior distribution). However, in reality, the distribution of the data is often not available or very complex, so the calculation of theoretical error rate is very difficult, so it is impossible to evaluate the performance of the algorithm directly based on it. Even in the case of normal distribution, it is difficult to calculate the error rate. It is impossible to give a complete analytical solution. It can only be calculated by looking up the table. The results of two kinds of normal cases with equal covariance are shown as follows:(5)Dx=gWdI+δd,Ex=∑k=1K∑i∈Ckxi−uk2.Therefore, many common error rate estimation methods based on data estimation are proposed. The minimum error rate measureW is essentially the minimum risk measure under 0-1 loss:(6)GLX=−∑∀Wa∈APWa|Wlog2Wa|W,where l is the 0-1 loss and G(x) is the predicted category. The optimal solution of this problem is called Bayesian classifier, which is the theoretically optimal solution. The error rate of Bayesian classification is called Bayesian rate. It also has the problem of theoretical analytical solutions due to the inability to obtain the data distribution. The simplest error rate estimation is the training error rate. The error rate is estimated by the percentage of classification errors (the percentage of samples with classification errors in the total training samples) in the training data:(7)Dik=∑anτ1Xik+∑bnτ2UYik+Bik,where B is the total number of training samples, u is the indicative function, when the classification is wrong, it is 1, when it is correct, it is 0, and X is the prediction function of the category. However, it is a pity that the training error rate is an optimistic estimate of the error rate. Even in extreme cases, the training error rate can be strictly zero by having the classifier remember the category of each training sample. However, the performance of such a classification algorithm cannot represent its performance on new data, and it often performs poorly on new samples that are not observed.


## 2.1. Thyroid Cancer Detection Index

Thyroid cancer accounts for about 3.8% of the world’s cancer-related diseases, with a latent period of 5–10 years and no symptoms. Most of them can be cured, especially the prognosis of the thyroid is the best, but early lymph node metastasis and tumor invasion often occur. Although the cure rate and mortality rate of patients are decreasing, the incidence rate is still increasing [11]. Therefore, it is necessary to explore the early detection, clinical analysis, and prognostic indicators of thyroid cancer [12]. A large number of studies have shown that TRPC5, as a Ca2+ channel, participates in the occurrence of many malignant tumors, which mainly mediates Ca2+ imbalance by triggering the Ca2+ entry pathway or changing membrane polarization, thus promoting the occurrence of malignant tumors [13]. Chemical resistance is the main feature of a malignant tumor. TRPC5 with abnormally high expression in breast cancer promotes the activity of the Ca2+ channel, and the Ca2+ signal activates transcription factor NFATC3 to start the transcription of P-glycoprotein, resulting in chemical resistance [14]. In colon cancer, TRPC5 activates the TAP signaling pathway by promoting hypoxia- inducible factor-1α expression to induce epithelial-mesenchymal transition and promote tumor metastasis [15]. TAP may hurt the clinicopathological characteristics of the thyroid and may lead to a worse prognosis [16].Abnormal glycosylated protein (TAP) is a sensitive indicator to evaluate the metastasis or recurrence of thyroid cancer, which plays an indispensable role in the early screening, treatment, and prognosis of patients with thyroid cancer. However, to a certain extent, some factors may interfere with the TAP level in patients, resulting in the false positive or false negative in clinical detection [17]. On the contrary, for thyroid cancer patients with relatively late diagnosis, the serum carcinoembryonic antigen (CEA) level will increase in varying degrees, while the TAP level will be at a low level [18]. To explore the value of serum TAP combined with CEA in risk assessment and early screening of thyroid cancer, the serum TAP and CEA levels and diagnostic indexes of different groups were detected and compared by the electrochemiluminescence method [19]. In addition, overexpression of TAP can also effectively improve the activity of vasculogenic mimicry-related proteins and ultimately enhance the vascular invasion of hepatocellular carcinoma [20]. TAP family is widely involved in the development of tumors. However, up to now, there are few reports on the relationship between the TAP family and thyroid cancer [21]. MTAP is an important member of the TAP family. According to the data of the NCBI (National Center for Biotechnology Information), the expression of MTAP in normal thyroid tissue is significantly higher than that in other organs and tissues [22]. Patients with Graves’ disease have a higher risk of thyroid disease, and the thyroid in patients with Graves’ disease shows a higher ability of invasion and metastasis [23]. This suggests that there is a certain correlation between MTAP and thyroid [24]. This study first revealed the correlation between MTAP and thyroid through bioinformatics mining and analysis [25]. To further verify the conclusion, real-time PCR and western blotting were used to detect the expression of MTAP. The expression of MTAP in thyroid tissue was significantly lower than that in adjacent tissues, and the expression of MTAP in claim-bearing thyroid tissue was also significantly lower than that in thyroid tissue without claim. Based on this, we preliminarily infer that MTAP may be a tumor suppressor gene of the thyroid. The expression of MTAP in thyroid tissues was significantly lower than that in adjacent tissues, and the expression of MTAP was related to cervical lymph node metastasis. This suggests that the upregulation of MTAP expression may inhibit the proliferation of thyroid cells and lymph node metastasis. MTAP is expected to become a new biological target and provide a new direction for the diagnosis, treatment, and prevention of thyroid recurrence.


## 2.2. Diagnostic Index Analysis Algorithm

In the problem of the serum evaluation index, people often want to reduce the classification errors as much as possible. Based on this goal, we can measure the performance of the classification algorithm. Suppose there areC categories in the classification problem, and the states of each category are expressed as i1,...,ic; PiandPx are prior probabilities, a class-conditional probability density function of the occurrence of class I is represented, Dx represents the d-dimensional feature vector, and the goal of classification is to predict the category of serum indicators based on this feature vector. The so-called error rate refers to the average error rate.(1)DxgainY=Px−avgσY′,σicσY,Pxwkt=ω1dkc+ω2dkc+ω3TkNcK+ω1PKcK.There are two types of classification:(2)Dκ=2kk+1+12+12kc2−c132+2c2−c13.If the feature space is divided into two types by the discriminant function, they are as follows:(3)Pxi,wj=PdiPwj|di;Pwj|di=∑k=1KPwj|zkPzk|di.Among them,R1andR2 are divided into two regions. Correspondingly, for the multiclass classification problem, if we divide the feature space into C regions, the average error rate based on these C regions is E:(4)ER1,R2=log2PR1&R2PR1PR2.It can be seen from equation (4) that the calculation of error rate depends on the distribution of data (including prior distribution). However, in reality, the distribution of the data is often not available or very complex, so the calculation of theoretical error rate is very difficult, so it is impossible to evaluate the performance of the algorithm directly based on it. Even in the case of normal distribution, it is difficult to calculate the error rate. It is impossible to give a complete analytical solution. It can only be calculated by looking up the table. The results of two kinds of normal cases with equal covariance are shown as follows:(5)Dx=gWdI+δd,Ex=∑k=1K∑i∈Ckxi−uk2.Therefore, many common error rate estimation methods based on data estimation are proposed. The minimum error rate measureW is essentially the minimum risk measure under 0-1 loss:(6)GLX=−∑∀Wa∈APWa|Wlog2Wa|W,where l is the 0-1 loss and G(x) is the predicted category. The optimal solution of this problem is called Bayesian classifier, which is the theoretically optimal solution. The error rate of Bayesian classification is called Bayesian rate. It also has the problem of theoretical analytical solutions due to the inability to obtain the data distribution. The simplest error rate estimation is the training error rate. The error rate is estimated by the percentage of classification errors (the percentage of samples with classification errors in the total training samples) in the training data:(7)Dik=∑anτ1Xik+∑bnτ2UYik+Bik,where B is the total number of training samples, u is the indicative function, when the classification is wrong, it is 1, when it is correct, it is 0, and X is the prediction function of the category. However, it is a pity that the training error rate is an optimistic estimate of the error rate. Even in extreme cases, the training error rate can be strictly zero by having the classifier remember the category of each training sample. However, the performance of such a classification algorithm cannot represent its performance on new data, and it often performs poorly on new samples that are not observed.


## 3. Experimental Design

### 3.1. Research Objects

From January 2019 to June 2021, 400 patients with thyroid nodules above class IV confirmed by a physical examination in the health management center of our hospital were included in the study. B-ultrasound-guided thyroid nodule puncture and pathological examination confirmed thyroid cancer. The inclusion and exclusion criteria were as follows:(1)
The age range is 20–79 years(2)
The diagnosis of thyroid cancer was based on the relevant standards of the guidelines for diagnosis and treatment of thyroid nodules and differentiated thyroid cancer issued by the Chinese Medical Association(3)
All patients with thyroid cancer were confirmed by pathological examination(4)
The patient did not receive chemoradiotherapy(5)
All patients and their families were informed of the study, and the study was approved by the ethics committee of our hospitalSerious heart, liver, and kidney dysfunction or mental disorders, diabetes mellitus (high glycosylated hemoglobin), fracture, pregnancy, autoimmune diseases, and other results were not included in the assessment indicators. The grouping is shown in Table1.Table 1
Thyroid cancer patient group information.
GroupMaleFemaleSample size of the positive groupAgeAverage ageNormal group415910029–7958.0 ± 23.2CEA positive group376310028–7953.0 ± 20.3TAP positive group495110038–6953.5 ± 12.4CEA + TAP positive465410038–7657.3 ± 14.9


### 3.2. Determination Method

#### 3.2.1. TAP Determination

First, 5 ml of fasting venous blood was collected from all patients after admission, which was evenly dropped onto two slides, and then placed on the horizontal operating platform to dry under natural conditions. Secondly, the dried test pieces were placed under constant temperature and humidity for 10 minutes. Then, a dropper was used to absorb the upper layer of the reagent after shaking and drop it vertically onto the test piece. After the test piece forms original “spots,” the specimen can be made.Then, using the integrated film reader microscope, in general, the achromatic objective was used to observe the three spots under the specimen on the display screen and to find the specific form of condensate in the spots. The TAP detection system was used to take particle pictures, and the software area was used to measure the particle size and record.


#### 3.2.2. Determination of CEA

First, 5 ml of fasting venous blood was collected from all patients after admission, and then 2 ml of sodium citrate anticoagulant was added, then centrifuged for 10 min with a centrifuge (speed: 2500r/min) to achieve serum separation, and stored at minus 80°C for subsequent detection. Serum CEA was detected by an automatic chemiluminescence immunoassay analyzer (manufacturer model: DPC Immulite 1000) and its matching detection reagent. The whole detection operation strictly followed the instructions. The test shall be carried out in strict accordance with the instruction manual of the instrument to avoid errors.


#### 3.2.3. TAP + CEA Detection Method

The two detection method areas above and the two detection methods are combined with statistics.


### 3.3. Judgment and Statistics of Inspection Results

TAP negative (−): loose sand and snowflake-like small dark brown particles can be seen, and the aggregate area is less than 121µm2.TAP positive (+): area ≥121µm2 agglomerate particles is visible, the shape is oval, round, and polygonal, and agglomerate particles show a certain degree of shading.CEA negative (−): visible condensate area ≤3.5 ng/ml.CEA positive (+): value > 3.5 ng/ml was positive.Serum TAP, serum CEA, and serum TAP + CEA were detected in all subjects, and the missed diagnosis rate and misdiagnosis rate of the three methods were compared.SPSS software was used to analyze the above data. Independent sampleT-test was used to compare continuous variables between groups, and Fisher’s exact test or X2 test was used to compare categorical variables. Bilateral test P < 0.05 showed that the difference was statistically significant.


## 3.1. Research Objects

From January 2019 to June 2021, 400 patients with thyroid nodules above class IV confirmed by a physical examination in the health management center of our hospital were included in the study. B-ultrasound-guided thyroid nodule puncture and pathological examination confirmed thyroid cancer. The inclusion and exclusion criteria were as follows:(1)
The age range is 20–79 years(2)
The diagnosis of thyroid cancer was based on the relevant standards of the guidelines for diagnosis and treatment of thyroid nodules and differentiated thyroid cancer issued by the Chinese Medical Association(3)
All patients with thyroid cancer were confirmed by pathological examination(4)
The patient did not receive chemoradiotherapy(5)
All patients and their families were informed of the study, and the study was approved by the ethics committee of our hospitalSerious heart, liver, and kidney dysfunction or mental disorders, diabetes mellitus (high glycosylated hemoglobin), fracture, pregnancy, autoimmune diseases, and other results were not included in the assessment indicators. The grouping is shown in Table1.Table 1
Thyroid cancer patient group information.
GroupMaleFemaleSample size of the positive groupAgeAverage ageNormal group415910029–7958.0 ± 23.2CEA positive group376310028–7953.0 ± 20.3TAP positive group495110038–6953.5 ± 12.4CEA + TAP positive465410038–7657.3 ± 14.9


## 3.2. Determination Method

### 3.2.1. TAP Determination

First, 5 ml of fasting venous blood was collected from all patients after admission, which was evenly dropped onto two slides, and then placed on the horizontal operating platform to dry under natural conditions. Secondly, the dried test pieces were placed under constant temperature and humidity for 10 minutes. Then, a dropper was used to absorb the upper layer of the reagent after shaking and drop it vertically onto the test piece. After the test piece forms original “spots,” the specimen can be made.Then, using the integrated film reader microscope, in general, the achromatic objective was used to observe the three spots under the specimen on the display screen and to find the specific form of condensate in the spots. The TAP detection system was used to take particle pictures, and the software area was used to measure the particle size and record.


### 3.2.2. Determination of CEA

First, 5 ml of fasting venous blood was collected from all patients after admission, and then 2 ml of sodium citrate anticoagulant was added, then centrifuged for 10 min with a centrifuge (speed: 2500r/min) to achieve serum separation, and stored at minus 80°C for subsequent detection. Serum CEA was detected by an automatic chemiluminescence immunoassay analyzer (manufacturer model: DPC Immulite 1000) and its matching detection reagent. The whole detection operation strictly followed the instructions. The test shall be carried out in strict accordance with the instruction manual of the instrument to avoid errors.


### 3.2.3. TAP + CEA Detection Method

The two detection method areas above and the two detection methods are combined with statistics.


## 3.2.1. TAP Determination

First, 5 ml of fasting venous blood was collected from all patients after admission, which was evenly dropped onto two slides, and then placed on the horizontal operating platform to dry under natural conditions. Secondly, the dried test pieces were placed under constant temperature and humidity for 10 minutes. Then, a dropper was used to absorb the upper layer of the reagent after shaking and drop it vertically onto the test piece. After the test piece forms original “spots,” the specimen can be made.Then, using the integrated film reader microscope, in general, the achromatic objective was used to observe the three spots under the specimen on the display screen and to find the specific form of condensate in the spots. The TAP detection system was used to take particle pictures, and the software area was used to measure the particle size and record.


## 3.2.2. Determination of CEA

First, 5 ml of fasting venous blood was collected from all patients after admission, and then 2 ml of sodium citrate anticoagulant was added, then centrifuged for 10 min with a centrifuge (speed: 2500r/min) to achieve serum separation, and stored at minus 80°C for subsequent detection. Serum CEA was detected by an automatic chemiluminescence immunoassay analyzer (manufacturer model: DPC Immulite 1000) and its matching detection reagent. The whole detection operation strictly followed the instructions. The test shall be carried out in strict accordance with the instruction manual of the instrument to avoid errors.


## 3.2.3. TAP + CEA Detection Method

The two detection method areas above and the two detection methods are combined with statistics.


## 3.3. Judgment and Statistics of Inspection Results

TAP negative (−): loose sand and snowflake-like small dark brown particles can be seen, and the aggregate area is less than 121µm2.TAP positive (+): area ≥121µm2 agglomerate particles is visible, the shape is oval, round, and polygonal, and agglomerate particles show a certain degree of shading.CEA negative (−): visible condensate area ≤3.5 ng/ml.CEA positive (+): value > 3.5 ng/ml was positive.Serum TAP, serum CEA, and serum TAP + CEA were detected in all subjects, and the missed diagnosis rate and misdiagnosis rate of the three methods were compared.SPSS software was used to analyze the above data. Independent sampleT-test was used to compare continuous variables between groups, and Fisher’s exact test or X2 test was used to compare categorical variables. Bilateral test P < 0.05 showed that the difference was statistically significant.


## 4. Results and Discussion

### 4.1. Comparison of Clinical Data

According to the test results, 400 subjects were divided into the normal group (TAP/CEA negative) (100 cases), CEA positive group (100 cases), TAP positive group (100 cases), and TAP + CEA positive group (TAP/CEA positive) (100 cases), including 173 patients with thyroid cancer (malignant) and 227 patients with benign thyroid disease. The clinical data of each group are shown in Table2. There was no significant difference in gender, age, and pathological results among the four groups (P > 0.05).Table 2
Clinical data of each group of subjects (x ± s).
IndexNormal group (n = 100)CEA positive group (n = 100)TAP positive group (n = 100TAP + CEA positive group (n = 100)P valueGenderMale413751540.36Female59634946Average age (years)58.0 ± 23.253.0 ± 20.353.5 ± 12.457.3 ± 14.90.19Pathological resultsBenign1006646150.23Malignant03454851.00As shown in Figure1, the positive expression rate of TAP and CEA in serum of patients with thyroid cancer is more than 55%. Clinically, the typical manifestations are masses found in the thyroid, with uneven surface, fixed texture, and hard texture. When swallowing, the thyroid body moves up and down in a small range. In addition to the significant enlargement of the masses, thyroid cancer also has the characteristics of invasion of surrounding tissues. Therefore, the early screening of thyroid cancer has a very important positive significance for the timely and effective treatment of the disease. It can not only provide effective guidance for the radical resection of thyroid cancer but also reduce the detection rate of advanced malignant results to a certain extent.Figure 1
Seropositive expression rate in patients with thyroid cancer.


### 4.2. Serum TAP and CEA Levels and Positive Rate

The indicators of the CEA positive group, TAP positive group, and TAP + CEA positive aggregate area are shown in Figure2. High expression of CEA in thyroid cancer indicates that there is a certain correlation between serum CEA and thyroid cancer. In this study, TAPs combined with CEA were used to detect patients with thyroid cancer with class IV or higher thyroid nodules. Elevated levels of TAP and CEA in patients with thyroid cancer indicate that the combination of TAP and CEA can accurately assess thyroid classification and has some clinical significance for the prognosis of thyroid nodules. The image of the thyroid cancer model is shown in Figure 3.Figure 2
Index of positive aggregate area.Figure 3
Thyroid cancer model image.As shown in Tables3 and 4, compared with the normal group, the areas of the CEA positive group, TAP positive group, and TAP + CEA positive aggregates were much larger, and the expressions of serum TAP and CEA were significantly higher, with statistical significance (P < 0.05).Table 3
Serum TAP level and positive rate of each group (%,x ± s).
GroupNumber of casesAgglomerate area (mm2)TAP expressionPositive (+)Negative (−)Normal group10089.02 ± 6.790100CEA positive group100103.03 ± 9.87a4654TAP positive group100138.56 ± 12.25ab1000TAP + CEA positive100210.01 ± 15.81abc1000x2/t68.591P value0.001Compared with the normal group,aP < 0.05; compared with the CEA positive group, bP < 0.05; compared with the TAP positive group, cP < 0.05.Table 4
Serum CEA level and positive rate (%,X ± s).
GroupNumber of casesNumerical value (ng/ml)CEA expressionPositive (+)Negative (−)Normal group1001.00 ± 0.230100CEA positive group1002.54 ± 0.31a6634TAP positive group1005.38 ± 0.51ab0100TAP + CEA positive10015.69 ± 4.01abc1000x2/t55.261P value0.001Compared with the normal group,aP < 0.05; compared with the CEA positive group, bP < 0.05; compared with the TAP positive group, cP < 0.05.As shown in Figure4, the serum CEA expression in thyroid cancer was significantly higher than that in patients with benign thyroid diseases, indicating that CEA may participate in the occurrence and development of malignant tumors. The results also show that the sensitivity and specificity of serum CEA in the diagnosis of thyroid cancer are 89.85% and 88.00%, indicating that CEA has an important specific marker role in thyroid cancer. The reason for the low diagnostic sensitivity may be related to the low activity and low release of CEA in the process of apoptosis or differentiation of early cancer cells. In conclusion, compared with TAP and CEA alone, serum TAP combined with CEA has higher early screening value in thyroid cancer. The pathological images of thyroid cancer in different groups are shown in Figure 5.Figure 4
Intuitive diagram of test items.Figure 5
Thyroid cancer pathology.As shown in Table5, the expression of TTF-1 and NIS in the CEA + TAP positive group increased, while the expression of PTEN decreased (P < 0.05).Table 5
Detection of TTF-1, PTEN, and NIS expression in each group (x¯±s).
GroupNormalCEA positiveTAP positiveCEA + TAP positiveFPTTF-10.59 ± 0.031.04 ± 0.02a1.32 ± 0.09ab1.98 ± 0.13abc57.2310.001PTEN1.70 ± 0.090.89 ± 0.06a0.56 ± 0.03ab0.30 ± 0.02abc76.8520.001NIS0.40 ± 0.060.79 ± 0.59a1.45 ± 0.15ab2.10 ± 0.19abc76.3210.001


### 4.3. Diagnostic Indexes

As shown in Figure6, the specific sensitivity of serum TAP in the diagnosis of thyroid cancer was 85.25%, the specific specificity was 85.06%, the AUC value under the ROC curve area was 0.605, the specific sensitivity of serum CEA in the diagnosis of thyroid cancer was 89.85%, the specific specificity was 88.00%, the AUC value under the ROC curve area was 0.627, the sensitivity of serum TAP combined with CEA in the diagnosis of thyroid cancer was 96.84%, the specificity was 96.79%, and the AUC value under the ROC curve area was 0.915. The variance processing is shown in Figure 7.Figure 6
Comparison of diagnostic sensitivity and specific ROC.Figure 7
Diagnostic indexes of serum TAP and CEA in the diagnosis of the benign and malignant thyroid.


### 4.4. Detection Rate of Thyroid Nodules

#### 4.4.1. Comparison of the Detection Rate of Different Detection Methods for Thyroid Nodules

From the comparison in Figure8, it can be concluded that the number of class IV thyroid nodules detected by TAP is much greater than that of class V, and the same is true for CEA; in addition, the number of class IV detected by TAP + CEA exceeds the number of class V thyroid nodules. The proportion is larger and statistically significant. The details are shown in Table 6.Figure 8
Detected type IV and V thyroid nodules.Table 6
Comparison of detection rates of thyroid nodules by different detection methods (n, (%)).
Detection meansClass IVClass VTAP testing363 (79.20)50 (9.00)CEA testing346 (86.25)60 (15.75)TAP + CEA testing390 (98.75)ab10 (2.45)abF36.16140.658P0.0010.001


#### 4.4.2. Comparison of Missed Diagnosis and Misdiagnosis among Three Detection Methods

It can be seen from the data analysis in Figure9 that there is no significant difference between the results of the CEA experiment. Compared with the other two, TAP + CEA has a lower rate of misdiagnosis and missed diagnosis. The details are shown in Table 7.Figure 9
Missed diagnosis rate and misdiagnosis rate of the serum test.Table 7
Comparison of the missed diagnosis and misdiagnosis rate of three detection methods.
Detection meansTAP testCEA testTAP + CEA testFPMissed diagnosis46 (11.35)48 (11.65)9 (1.05)ab37.3210.001Misdiagnosis24 (5.65)26 (7.35)1.03 (0.26)ab39.4530.001Compared with TAP,aP < 0.05; compared with CEA detection, bP < 0.05.


#### 4.4.3. Comparison of Sensitivity, Specificity, and Accuracy of Three Detection Methods

As shown in Figure10, the sensitivities of TAP and CEA were 86.231% and 90.767%, respectively, with no significant difference (P > 0.05). The specificities of TAP and CEA were 86.026% and 89.217%, and the accuracies of TAP and CEA were 87.359% and 88.884% (P > 0.05); compared with TAP and CEA, TAP + CEA had higher sensitivity, specificity, and accuracy (P < 0.05). The sensitivity, specificity, and accuracy of TAP + CEA were 97.793%, 97.775%, and 98.689%. Detailed data are shown in Table 8.Figure 10
Comparison of sensitivity and specificity indicators.Table 8
Comparison of sensitivity, specificity, and accuracy of three detection methods.
Detection meansTAP testCEA testTAP + CEA testFPSensitivity86.23190.76797.783ab57.3210.001Specificity86.02689.21797.775ab35.6890.001Accuracy87.35988.88498.689ab47.6890.001Compared with TAP,aP < 0.05; compared with CEA detection, bP < 0.05.


### 4.5. Discussion

The results of this study show that the area of aggregates in patients with thyroid cancer is larger than that in patients with benign thyroid diseases, indicating that abnormal sugar chain glycoprotein (TAP) is constantly released in blood during the metabolism of thyroid cancer, resulting in significantly greater serum TAP expression than patients with benign thyroid diseases, consistent with related research results. In addition, the detection of thyroid cancer by TAP and CEA may have false negatives under certain circumstances. Given that it may be associated with decreased metabolism of cancer cells in patients with advanced thyroid cancer, decreased metabolism of cancer cells lowers serum TAP levels and develops TAP levels.In most cases, thyroid cancer has no significant clinical symptoms and signs in the early stage of its occurrence. Generally, thyroid masses will be found after cervical ultrasonography and thyroid palpation during physical examination. Currently, ultrasound examination is mainly used clinically to determine the risk of thyroid cancer. The occurrence of tumors is closely related to the abnormal expression of sugar chains. With the continuous changes of glycosylation, tumor cells will undergo a large number of proliferation processes.The results of this study found that the serum TAP and CEA expressions in patients with thyroid cancer were significantly higher, and the difference was statistically significant (P < 0.05). This indicates that TAP and CEA are all involved in the occurrence and development of malignant tumors. To a certain extent, the high expression of indicators can further promote the abnormal pathology of papillary cells or thyroid follicles through the influence of some factors.The treatment and prognosis of benign and malignant thyroid nodules are completely different, and accurate and timely judgments can be made. Early-stage cancers are caused by various chronic diseases and abnormal signs. Therefore, it is of great significance to carry out targeted screening for patients with chronic diseases and abnormal signs of tumor risk.


## 4.1. Comparison of Clinical Data

According to the test results, 400 subjects were divided into the normal group (TAP/CEA negative) (100 cases), CEA positive group (100 cases), TAP positive group (100 cases), and TAP + CEA positive group (TAP/CEA positive) (100 cases), including 173 patients with thyroid cancer (malignant) and 227 patients with benign thyroid disease. The clinical data of each group are shown in Table2. There was no significant difference in gender, age, and pathological results among the four groups (P > 0.05).Table 2
Clinical data of each group of subjects (x ± s).
IndexNormal group (n = 100)CEA positive group (n = 100)TAP positive group (n = 100TAP + CEA positive group (n = 100)P valueGenderMale413751540.36Female59634946Average age (years)58.0 ± 23.253.0 ± 20.353.5 ± 12.457.3 ± 14.90.19Pathological resultsBenign1006646150.23Malignant03454851.00As shown in Figure1, the positive expression rate of TAP and CEA in serum of patients with thyroid cancer is more than 55%. Clinically, the typical manifestations are masses found in the thyroid, with uneven surface, fixed texture, and hard texture. When swallowing, the thyroid body moves up and down in a small range. In addition to the significant enlargement of the masses, thyroid cancer also has the characteristics of invasion of surrounding tissues. Therefore, the early screening of thyroid cancer has a very important positive significance for the timely and effective treatment of the disease. It can not only provide effective guidance for the radical resection of thyroid cancer but also reduce the detection rate of advanced malignant results to a certain extent.Figure 1
Seropositive expression rate in patients with thyroid cancer.


## 4.2. Serum TAP and CEA Levels and Positive Rate

The indicators of the CEA positive group, TAP positive group, and TAP + CEA positive aggregate area are shown in Figure2. High expression of CEA in thyroid cancer indicates that there is a certain correlation between serum CEA and thyroid cancer. In this study, TAPs combined with CEA were used to detect patients with thyroid cancer with class IV or higher thyroid nodules. Elevated levels of TAP and CEA in patients with thyroid cancer indicate that the combination of TAP and CEA can accurately assess thyroid classification and has some clinical significance for the prognosis of thyroid nodules. The image of the thyroid cancer model is shown in Figure 3.Figure 2
Index of positive aggregate area.Figure 3
Thyroid cancer model image.As shown in Tables3 and 4, compared with the normal group, the areas of the CEA positive group, TAP positive group, and TAP + CEA positive aggregates were much larger, and the expressions of serum TAP and CEA were significantly higher, with statistical significance (P < 0.05).Table 3
Serum TAP level and positive rate of each group (%,x ± s).
GroupNumber of casesAgglomerate area (mm2)TAP expressionPositive (+)Negative (−)Normal group10089.02 ± 6.790100CEA positive group100103.03 ± 9.87a4654TAP positive group100138.56 ± 12.25ab1000TAP + CEA positive100210.01 ± 15.81abc1000x2/t68.591P value0.001Compared with the normal group,aP < 0.05; compared with the CEA positive group, bP < 0.05; compared with the TAP positive group, cP < 0.05.Table 4
Serum CEA level and positive rate (%,X ± s).
GroupNumber of casesNumerical value (ng/ml)CEA expressionPositive (+)Negative (−)Normal group1001.00 ± 0.230100CEA positive group1002.54 ± 0.31a6634TAP positive group1005.38 ± 0.51ab0100TAP + CEA positive10015.69 ± 4.01abc1000x2/t55.261P value0.001Compared with the normal group,aP < 0.05; compared with the CEA positive group, bP < 0.05; compared with the TAP positive group, cP < 0.05.As shown in Figure4, the serum CEA expression in thyroid cancer was significantly higher than that in patients with benign thyroid diseases, indicating that CEA may participate in the occurrence and development of malignant tumors. The results also show that the sensitivity and specificity of serum CEA in the diagnosis of thyroid cancer are 89.85% and 88.00%, indicating that CEA has an important specific marker role in thyroid cancer. The reason for the low diagnostic sensitivity may be related to the low activity and low release of CEA in the process of apoptosis or differentiation of early cancer cells. In conclusion, compared with TAP and CEA alone, serum TAP combined with CEA has higher early screening value in thyroid cancer. The pathological images of thyroid cancer in different groups are shown in Figure 5.Figure 4
Intuitive diagram of test items.Figure 5
Thyroid cancer pathology.As shown in Table5, the expression of TTF-1 and NIS in the CEA + TAP positive group increased, while the expression of PTEN decreased (P < 0.05).Table 5
Detection of TTF-1, PTEN, and NIS expression in each group (x¯±s).
GroupNormalCEA positiveTAP positiveCEA + TAP positiveFPTTF-10.59 ± 0.031.04 ± 0.02a1.32 ± 0.09ab1.98 ± 0.13abc57.2310.001PTEN1.70 ± 0.090.89 ± 0.06a0.56 ± 0.03ab0.30 ± 0.02abc76.8520.001NIS0.40 ± 0.060.79 ± 0.59a1.45 ± 0.15ab2.10 ± 0.19abc76.3210.001


## 4.3. Diagnostic Indexes

As shown in Figure6, the specific sensitivity of serum TAP in the diagnosis of thyroid cancer was 85.25%, the specific specificity was 85.06%, the AUC value under the ROC curve area was 0.605, the specific sensitivity of serum CEA in the diagnosis of thyroid cancer was 89.85%, the specific specificity was 88.00%, the AUC value under the ROC curve area was 0.627, the sensitivity of serum TAP combined with CEA in the diagnosis of thyroid cancer was 96.84%, the specificity was 96.79%, and the AUC value under the ROC curve area was 0.915. The variance processing is shown in Figure 7.Figure 6
Comparison of diagnostic sensitivity and specific ROC.Figure 7
Diagnostic indexes of serum TAP and CEA in the diagnosis of the benign and malignant thyroid.


## 4.4. Detection Rate of Thyroid Nodules

### 4.4.1. Comparison of the Detection Rate of Different Detection Methods for Thyroid Nodules

From the comparison in Figure8, it can be concluded that the number of class IV thyroid nodules detected by TAP is much greater than that of class V, and the same is true for CEA; in addition, the number of class IV detected by TAP + CEA exceeds the number of class V thyroid nodules. The proportion is larger and statistically significant. The details are shown in Table 6.Figure 8
Detected type IV and V thyroid nodules.Table 6
Comparison of detection rates of thyroid nodules by different detection methods (n, (%)).
Detection meansClass IVClass VTAP testing363 (79.20)50 (9.00)CEA testing346 (86.25)60 (15.75)TAP + CEA testing390 (98.75)ab10 (2.45)abF36.16140.658P0.0010.001


### 4.4.2. Comparison of Missed Diagnosis and Misdiagnosis among Three Detection Methods

It can be seen from the data analysis in Figure9 that there is no significant difference between the results of the CEA experiment. Compared with the other two, TAP + CEA has a lower rate of misdiagnosis and missed diagnosis. The details are shown in Table 7.Figure 9
Missed diagnosis rate and misdiagnosis rate of the serum test.Table 7
Comparison of the missed diagnosis and misdiagnosis rate of three detection methods.
Detection meansTAP testCEA testTAP + CEA testFPMissed diagnosis46 (11.35)48 (11.65)9 (1.05)ab37.3210.001Misdiagnosis24 (5.65)26 (7.35)1.03 (0.26)ab39.4530.001Compared with TAP,aP < 0.05; compared with CEA detection, bP < 0.05.


### 4.4.3. Comparison of Sensitivity, Specificity, and Accuracy of Three Detection Methods

As shown in Figure10, the sensitivities of TAP and CEA were 86.231% and 90.767%, respectively, with no significant difference (P > 0.05). The specificities of TAP and CEA were 86.026% and 89.217%, and the accuracies of TAP and CEA were 87.359% and 88.884% (P > 0.05); compared with TAP and CEA, TAP + CEA had higher sensitivity, specificity, and accuracy (P < 0.05). The sensitivity, specificity, and accuracy of TAP + CEA were 97.793%, 97.775%, and 98.689%. Detailed data are shown in Table 8.Figure 10
Comparison of sensitivity and specificity indicators.Table 8
Comparison of sensitivity, specificity, and accuracy of three detection methods.
Detection meansTAP testCEA testTAP + CEA testFPSensitivity86.23190.76797.783ab57.3210.001Specificity86.02689.21797.775ab35.6890.001Accuracy87.35988.88498.689ab47.6890.001Compared with TAP,aP < 0.05; compared with CEA detection, bP < 0.05.


## 4.4.1. Comparison of the Detection Rate of Different Detection Methods for Thyroid Nodules

From the comparison in Figure8, it can be concluded that the number of class IV thyroid nodules detected by TAP is much greater than that of class V, and the same is true for CEA; in addition, the number of class IV detected by TAP + CEA exceeds the number of class V thyroid nodules. The proportion is larger and statistically significant. The details are shown in Table 6.Figure 8
Detected type IV and V thyroid nodules.Table 6
Comparison of detection rates of thyroid nodules by different detection methods (n, (%)).
Detection meansClass IVClass VTAP testing363 (79.20)50 (9.00)CEA testing346 (86.25)60 (15.75)TAP + CEA testing390 (98.75)ab10 (2.45)abF36.16140.658P0.0010.001


## 4.4.2. Comparison of Missed Diagnosis and Misdiagnosis among Three Detection Methods

It can be seen from the data analysis in Figure9 that there is no significant difference between the results of the CEA experiment. Compared with the other two, TAP + CEA has a lower rate of misdiagnosis and missed diagnosis. The details are shown in Table 7.Figure 9
Missed diagnosis rate and misdiagnosis rate of the serum test.Table 7
Comparison of the missed diagnosis and misdiagnosis rate of three detection methods.
Detection meansTAP testCEA testTAP + CEA testFPMissed diagnosis46 (11.35)48 (11.65)9 (1.05)ab37.3210.001Misdiagnosis24 (5.65)26 (7.35)1.03 (0.26)ab39.4530.001Compared with TAP,aP < 0.05; compared with CEA detection, bP < 0.05.


## 4.4.3. Comparison of Sensitivity, Specificity, and Accuracy of Three Detection Methods

As shown in Figure10, the sensitivities of TAP and CEA were 86.231% and 90.767%, respectively, with no significant difference (P > 0.05). The specificities of TAP and CEA were 86.026% and 89.217%, and the accuracies of TAP and CEA were 87.359% and 88.884% (P > 0.05); compared with TAP and CEA, TAP + CEA had higher sensitivity, specificity, and accuracy (P < 0.05). The sensitivity, specificity, and accuracy of TAP + CEA were 97.793%, 97.775%, and 98.689%. Detailed data are shown in Table 8.Figure 10
Comparison of sensitivity and specificity indicators.Table 8
Comparison of sensitivity, specificity, and accuracy of three detection methods.
Detection meansTAP testCEA testTAP + CEA testFPSensitivity86.23190.76797.783ab57.3210.001Specificity86.02689.21797.775ab35.6890.001Accuracy87.35988.88498.689ab47.6890.001Compared with TAP,aP < 0.05; compared with CEA detection, bP < 0.05.


## 4.5. Discussion

The results of this study show that the area of aggregates in patients with thyroid cancer is larger than that in patients with benign thyroid diseases, indicating that abnormal sugar chain glycoprotein (TAP) is constantly released in blood during the metabolism of thyroid cancer, resulting in significantly greater serum TAP expression than patients with benign thyroid diseases, consistent with related research results. In addition, the detection of thyroid cancer by TAP and CEA may have false negatives under certain circumstances. Given that it may be associated with decreased metabolism of cancer cells in patients with advanced thyroid cancer, decreased metabolism of cancer cells lowers serum TAP levels and develops TAP levels.In most cases, thyroid cancer has no significant clinical symptoms and signs in the early stage of its occurrence. Generally, thyroid masses will be found after cervical ultrasonography and thyroid palpation during physical examination. Currently, ultrasound examination is mainly used clinically to determine the risk of thyroid cancer. The occurrence of tumors is closely related to the abnormal expression of sugar chains. With the continuous changes of glycosylation, tumor cells will undergo a large number of proliferation processes.The results of this study found that the serum TAP and CEA expressions in patients with thyroid cancer were significantly higher, and the difference was statistically significant (P < 0.05). This indicates that TAP and CEA are all involved in the occurrence and development of malignant tumors. To a certain extent, the high expression of indicators can further promote the abnormal pathology of papillary cells or thyroid follicles through the influence of some factors.The treatment and prognosis of benign and malignant thyroid nodules are completely different, and accurate and timely judgments can be made. Early-stage cancers are caused by various chronic diseases and abnormal signs. Therefore, it is of great significance to carry out targeted screening for patients with chronic diseases and abnormal signs of tumor risk.


## 5. Conclusions

This article draws the final conclusion through experimental comparison, TAP + CEA combined detection improves the diagnostic efficiency of the thyroid, while the missed diagnosis rate and misdiagnosis rate are reduced. In conclusion, the use of combined TAP and CEA detection of thyroid nodules in patients of class IV and above can improve the detection rate of thyroid cancer, reduce the missed diagnosis rate and misdiagnosis rate, and reduce the risk of thyroid cancer, which is important. It has implications for early diagnosis, treatment, and prognosis of thyroid cancer. However, there are still some deficiencies in this study, and the specific biological mechanisms of TAP in thyroid cells, such as expression regulation and action pathway, need to be further studied.



---

*Source: 8836288-2021-08-11.xml*