Innovative diagnostic approaches: Serum protein markers in renal cell carcinoma.

560 Background: In the era of precision medicine, we pursue less invasive, more powerful methods for screening, response prediction, and recurrence detection. While liquid biopsy has proven useful in other malignancies, similar diagnostic and prognostic tools for renal cell carcinoma (RCC) remain to be elucidated. We therefore aimed to investigate serum protein expression in patients before their RCC diagnosis vs. non-cancer controls to identify protein-cancer associations likely to have a role in cancer development and progression. Methods: Utilizing UK Biobank, we analyzed proteomic data in patients previously diagnosed with RCC (n=2245) vs. patients without RCC at time of serum collection who were later diagnosed (n=1225) vs. a cohort of non-cancer controls (n=44386). We estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional regression models. We investigated protein and RCC cancer-risk associations to examine the effects of reverse causality and conducted analyses to generate area under the curve (AUC) values to evaluate diagnostic performance of biomarkers. Results: We identified associations between elevated levels of tafa5, klk11, klk8, csdn, and clmp proteins and undiagnosed RCC. Highly expressed proteins in each cohort showed increased HR for cancer association (95% CI), with tafa5 exhibiting the highest HR in the treated group HR 9.7 (95%CI 6.3-12.0;p<0.00). Receiver operating characteristic curve demonstrated strong predictive capabilities: igfbp4 (AUC 0.9127;SN 0.8056;SP 0.8606), tafa5 (AUC 0.9134;SN 0.7500;SP 0.8996), tgfbr2 (AUC 0.9057;SN 0.6667;SP 0.9083), scarb2 (AUC 0.8968;SN 0.7500;SP 0.9197), nectin4 (AUC 0.9269;SN 0.7222;SP 0.9299) in the treated group. These findings indicate that specific proteomic biomarkers may have a significant association with RCC diagnosis, with high AUC values supporting their potential utility in RCC diagnosis and prognosis. Prospective validation in clinical settings is warranted. Conclusions: Our study highlights distinct protein elevations between patients presenting with RCC vs. those who were later diagnosed. Although further studies are warranted, the favorable HR, AUC, SN, and SP values for several proteins identified here underscore their potential as biomarkers for RCC diagnosis and prognosis.