Novel Biomarkers of Hypoxia and Metabolism in Clear Cell Renal Cell Carcinoma

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.