Clinical trial NCT05214885: Novel Biomarkers of Hypoxia and Metabolism in Clear Cell Renal Cell Carcinoma
Official title: Novel Biomarkers of Hypoxia and Metabolism in Clear Cell Renal Cell Carcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: clear cell renal cell carcinoma
carbonic anhydrase IX
HILPDA
NDUFA4L2
ANGPTL4
Cell-free DNA methylomes
EGLN3
Lead sponsor: Qianfoshan Hospital
Sponsor class: OTHER
First posted: 2022-01-31
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patient was preliminarily diagnosed as renal carcinoma by imaging examination and finally diagnosed as clear cell renal cell carcinoma by pathology. The patient was treated normally and no intervention was required in this study.

There is no need to collect additional samples. A small part of the remaining samples from routine biochemical and pathological tests of patients can be enough to complete the detections required by the study.

Brief summary: Renal cell carcinoma (RCC) is one of the common malignant tumors in human beings and originates from the renal tubular epithelium. Clear cell renal cell carcinoma (ccRCC) is the main pathological type of RCC. Due to the lack of reliable biomarkers and clinical symptoms for early diagnosis, imaging findings such as ultrasound and CT are needed. When the patients presented typical symptoms, for example, hematuria, backache, and abdominal mass, some of them are in advanced stages of cancer. About a quarter of patients had metastasis at the first diagnosis, and the 5-year survival rate of these patients was less than 10%. Therefore, the early diagnosis of ccRCC and the prevention of tumor recurrence and metastasis are of great significance.

The preliminary studies suggested that some hypoxia and metabolism-related molecules were highly expressed in ccRCC tumors but low in normal kidney tissues. The molecules included carbonic anhydrase IX/9 (CA IX/CA9), the mitochondrial NADH dehydrogenase \[ubiquinone\] 1 alpha subcomplex, 4-like 2(NDUFA4L2), angiopoietin-like protein 4(ANGPTL4), hypoxia inducible lipid droplet-associated (HILPDA）, and egl-9 family hypoxia-inducible factor 3( EGLN3) et al . Cell-free DNA methylomes were also highly expressed in the blood of ccRCC patients.

In order to further verify the expression status of the above novel biomarkers in ccRCC, the investigators will detect the expressions of these molecules in the tumor and adjacent tissues from 140 ccRCC patients by RT-PCR, Western blot, and immunohistochemistry.140 healthy people were selected as the control group. 30 patients with benign kidney diseases were selected as another control group. Blood and urine samples from the ccRCC group and the control group were collected. The mRNA and protein levels of the above molecules in blood or urine samples were detected by qRT-PCR and ELISA. The correlation between the expression of the above new biomarkers and clinical data, such as early diagnosis, pathological grade, recurrence and metastasis, and survival time, was statistically analyzed. The above molecular changes were dynamically detected before surgery, 1 week, and 6 months after surgery. A receiver-operating characteristic curve (ROC) was used to determine the threshold value of these biomarkers for the diagnosis of renal clear cell carcinoma.

The study is to explore the specific tumor biomarker spectrum for clinical diagnosis, evaluation of recurrence, metastasis, and prognosis of ccRCC, which will be auxiliary early screening and diagnosis, reducing the harm of renal cancer to human health.


Eligibility criteria: Inclusion Criteria:

* The age and sex of the healthy control group were matched with that of ccRCC patient group. There was no tumor in the kidney or other parts of the body, and no tumor in the blood system. The healthy control group did not have any renal benign diseases, such as kidney stones, diabetic nephropathy, inflammation, and uremia. There are no inflammatory diseases in other parts of the body; the functions of the liver, kidney, and heart were normal.

Exclusion Criteria:

* The volunteer has tumors in the kidney or other parts of the body, or blood system tumors; The volunteer has benign kidney diseases, such as kidney stones, diabetic nephropathy, nephritis and uremia, etc; The patient has inflammatory disease elsewhere. If the volunteer has any one of the above diseases, it shall be excluded.

Primary outcomes:
measure: Detection of novel biomarkers in ccRCC patients before surgery
timeFrame: For ccRCC patients, these six novel biomarkers were detected 1 to 3 days before surgery
measure: Detection of novel biomarkers in ccRCC patients 1 week after surgery
timeFrame: For ccRCC patients, the detection of these biomarkers were completed within one week after surgery
measure: Detection of novel biomarkers in ccRCC patients at 6 months after surgery
timeFrame: For ccRCC patients, these six novel biomarkers were detected at 6 months postoperatively
measure: Detection of novel biomarkers in the control groups as baseline
timeFrame: For the healthy control group and the benign kidney disease group, the levels of these six biomarkers were detected as baseline.
Secondary outcomes:
Other outcomes:
Locations:
city: Jinan
country: China
facility: The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital
Study officials:
affiliation: The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital
name: Li Zhang, Dr.
role: PRINCIPAL_INVESTIGATOR
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