Significance of preoperative levels biomarkers TGF-β1 and CA 19-9 in distinguishing benign and malignant pancreatic neoplasms
Authors: Kryvoruchko I.A. , Lurin I. A. , Krasnoselskyi M.V. , Honcharova N.M. , Tamer A.A.M. Habib , Nessonova M.M. , Honcharov A.S. , Kuzmenko O.V. , Kolesnyk V.P. 
Published: January 2025

Background. The article is relevant to the subject matter. Benign and malignant neoplasms of the pancreas represent a significant challenge in clinical practice, largely due to the lack of early diagnostic tools and the aggressive nature of the disease. Pancreatic cancer represents the 12th most commonly diagnosed cancer and the 3rd leading cause of cancer mortality, accounting for approximately 3% of all new cancer cases and 6% of all cancer deaths worldwide. The prognosis is poor, largely due to the difficulty of detecting the disease early. Consequently, in developing disease management strategies that align with the principles of precision medicine, which considers the unique characteristics of each patient, research has concentrated on identifying reliable clinical biomarkers with high specificity and sensitivity. These biomarkers are intended to facilitate early diagnosis in patients exhibiting symptoms and early detection of the disease in asymptomatic individuals at elevated risk of developing pancreatic cancer. The differentiation between inflammatory and neoplastic pancreatic neoplasms represents a significant diagnostic challenge for surgeons.
Purpose – is to investigate TGF-β in the blood serum of patients with solid and cystic neoplasms of the pancreas and to evaluate the clinical significance of this cytokine together with CA 19-9 for the diagnosis of benign and malignant neoplasms.
Materials and methods. This was a retrospective, cross-sectional study that analysed 89 patients of varying age groups with benign and malignant pancreatic neoplasms who were hospitalised and underwent surgical intervention between January 2020 and May 2024. Design: The patients were divided into two groups, malignant and benign, based on the cytological and histological assessment of pancreatic lesions. This resulted in seven groups of patients with different pathologies, designated as groups 1–7. The concentration of TGF-β1 in the blood serum was determined using the DRG TGF-β1 enzyme-linked immunosorbent assay (ELISA) test system (Germany). The concentration of СA19-9 in the blood serum was investigated by enzyme-linked immunosorbent assay. The control group comprised healthy donors aged between 19 and 53 (group 8). The statistical significance of the differences in TGF-β1 and CA 19-9 levels between the seven groups of patients with different diagnoses and the control group, as well as between the three groups (control / benign / malignant pancreatic neoplasms), was determined based on the Kruskal–Wallis test at a confidence level of 95%. Given that the differences were statistically significant in all cases, further pairwise intergroup comparisons were required. These were performed using the Mann–Whitney test. The area under the ROC curve (AUC) was regarded as the primary indicator of the quality of discrimination based on the values of a biomarker. The optimal threshold values of TGF-β1 and CA 19-9 levels in the blood serum were identified to facilitate the detection of pancreatic neoplasia and to differentiate neoplasms according to their type. In seeking a threshold value, the objective was to identify the optimal point that would achieve the highest possible specificity and sensitivity of discrimination.
Results. The results demonstrated that the level of TGF-β1 was statistically significantly different across all types of pancreatic pathology, as indicated by the Kruskal-Wallis test (KW H (7.104) = 80.821, p < 0.0001). However, when comparing the levels of this indicator between groups using the Mann-Whitney test, notable differences were observed between patients with pancreatic cancer and all other pathologies and controls, except patients with mucinous malignant neoplasms of the gland. The highest TGF-β1 values were observed in mucinous cystic neoplasms among all groups with pancreatic malignancies. When the data were summarised by dividing patients with pancreatic neoplasms into two groups depending on the malignancy/benignity of the neoplasms, a statistically significantly higher level of TGF-β1 and CA 19-9 was confirmed in malignant neoplasms compared to benign ones. Both biomarkers demonstrated excellent discriminatory ability for all tasks. The area under the ROC curves indicates that TGF-β1 and CA 19-9 have high diagnostic value for determining the presence/absence of pancreatic neoplasms and distinguishing between malignant and benign neoplasms in the sample of patients used in the study. In distinguishing between benign and malignant pancreatic neoplasms, the CA 19-9 biomarker exhibited the highest specificity and sensitivity (with point estimates of 100%), while the TGF-β1 also demonstrated excellent discriminatory ability with a sensitivity of 92.6% (95% CI = (75.7; 99.1)%) and specificity of 93.5% (95% CI = (84.3; 98.2)%). The optimal threshold value for the stratification of patients with pancreatic malignancies is a TGF-β1 level of at least 109.8 ng/ml and a CA 19-9 level of 36.0 U/ml or more.
Conclusions. TGF-β1 can serve as a convenient indicator of the degree of immune suppression in patients with benign and malignant pancreatic neoplasms. It can be assumed that TGF-β1 has a profound effect on structural changes and remodelling of this organ, thereby playing a key role in the pathogenesis of fibrosis and potentiation of apoptosis in epithelial cells. High serum TGF-β1 levels may be associated with an unfavourable prognosis in patients with prostate cancer. The data obtained suggest that serum TGF-β1 is a valuable diagnostic indicator, which allows it to be used as an objective diagnostic criterion for solid pancreatic malignancies, with a cut-off value of at least 109.8 ng/ml, using this indicator together with the determination of CA 19-9 in the blood serum, with a cut-off value of 36.0 U/ml or more.