Serum Protein Markers in Clear Cell Renal Cell Carcinoma

BACKGROUND Renal Cell Carcinoma (RCC) is one of the most frequently diagnosed malignancies, yet non-invasive biomarkers for early detection and prognosis in RCC remain scarce. This study aims to identify serum protein markers predictive of clear cell RCC (ccRCC) development and prognostic of survival outcomes. METHODS Using the UK Biobank, a prospective cohort of >500,000 individuals, we analyzed serum proteomic data from participants who developed ccRCC after serum collection (Group 2), those diagnosed prior to serum collection (Group 1), and controls (Group 3). Proteomic measurements were performed using the Olink Proximity Extension Assay (PEA). Cox proportional hazards regression models estimated hazard ratios (HRs) for cancer risk and survival, adjusting for age, sex, BMI, smoking status, and renal function. Kaplan-Meier survival analysis evaluated prognostic markers. RESULTS: Five serum proteins—HAVCR1, REN, INHBB, NCR3LG1, and PGF—were significantly associated with future ccRCC development. HAVCR1 exhibited the strongest predictive performance (HR 5.1, 95% CI: 3.6–7.3, p<0.001; AUC 0.8756). Among all patients with ccRCC, NCR3LG1 (HR 2.6, 95% CI: 1.4–5.1, p<0.002), PGF (HR 2.2, 95% CI: 1.3–3.8, p<0.001), and GDF15 (HR 1.8, 95% CI: 1.1–2.8, p<0.02) were associated with reduced survival. CONCLUSION This study identifies HAVCR1 as a promising diagnostic biomarker for early ccRCC detection, with NCR3LG1, PGF, and GDF15 serving as potential prognostic markers. Further validation in independent cohorts is needed to facilitate clinical translation into diagnostic and prognostic tools for ccRCC. https://doi.org/10.52733/IKCS24-Proc-or3 KEYWORDS