CD276 is a potential biomarker for the diagnosis of clear cell renal cell carcinoma based on bioinformatic analysis and clinical cases

Renal cell carcinoma, a malignant tumor originating from the renal tubular epithelium, accounts for 2-3% of adult malignant tumors, and is the most lethal malignant tumor in the urinary system. Clear cell renal cell carcinoma (ccRCC) is the most common form, accounting for about 75%. Current treatment for renal cancer is primarily surgery, but research indicates that 25% of patients still experience distant metastasis post-surgery, posing a great threat to patients' lives. Current molecular targeting or immunotherapy offers limited help in increasing progression-free survival (PFS) in late-stage kidney cancer patients, usually maintaining about 12 months or even lower. Therefore, there's an urgent need to find new therapeutic targets that can effectively inhibit ccRCC invasion and metastasis. B7 homology 3 molecule (B7-H3, also known as CD276), a new member of the immune co-stimulatory molecule B7/CD28 family, has been proven to significantly inhibit T cell function, and is a classic immune checkpoint molecule. Studies have shown the expression of CD276 is related to the grading and prognosis of ccRCC, but the specific role and mechanism of CD276 in ccRCC are not yet fully understood. This study aims to clarify that CD276 expression level is higher in ccRCC tissue than in adjacent tissue by bioinformatic analysis. We hope to illustrate that CD276, through integrin-involved FAK activation, participates in ccRCC pathological changes by activating the MAPK pathway. CD276 expression level has a negative relationship with clinical pathological characteristics of ccRCC confirmed by histological level. CD276, through integrin-mediated FAK activation can promote ccRCC proliferation, invasion, and metastasis confirmed by cellular level. It can also stimulate tumor growth in nude mice experiment confirmed by animal level. This study attempts to prove the positive correlation between the CD276 expression in the tissues of ccRCC patients and the expression of FAK, which is related to negative clinical pathological features and poor prognosis. We also proved that in ccRCC, CD276 promotes tumour proliferation, metastasis, and invasion through the FAK-mediated MAPK pathway.