Platelet Count as an Independent Prognostic Marker in Clear Cell Renal Cell Carcinoma: Insights from Multi-source Data Analysis

Background: Clear Cell Renal Cell Carcinoma (ccRCC) is one of the most common and aggressive forms of kidney cancer, and identifying reliable prognostic indicators remains a critical challenge. While various biomarkers have been explored, platelet count has not been comprehensively evaluated as an independent prognostic factor in ccRCC. Given its clinical accessibility, platelet count could be a valuable tool for predicting patient outcomes. Objective: This study aims to evaluate the potential of platelet count as an independent prognostic marker for ccRCC patients using multi-source data analysis. Methods: We collected summary data from four large-scale genome-wide association studies (GWAS), constructed a bidirectional Mendelian randomization (MR) framework, used statistical methods such as inverse variance weighted (IVW), MR Egger regression, and weighted median, and analyzed the relationship between platelet count and the risk and prognosis of clear cell renal cell carcinoma (ccRCC) by propensity score matching to reduce selection bias. Then, we retrospectively collected clinical data from 231 ccRCC patients who underwent partial or radical nephrectomy at the First Affiliated Hospital of Anhui Medical University from 2014 to 2020 to verify the accuracy of the results. Results: We found through MR analysis that an increase in platelet count is positively correlated with the risk of kidney cancer (OR=1.001, 95% CI: 1.000-1.001, P=0.035). In 231 ccRCC patients, high platelet count was significantly correlated with later tumor staging (T, N, AJCC) and higher Fuhrman grade (P<0.05). In addition, in the TCGA cohort, the overall survival rate (OS) and disease-free survival rate (DFS) of patients with high platelet counts were significantly lower than those with low platelet counts (P<0.05). Patients with high platelet counts have a higher burden of tumor mutations, especially in key genes such as VHL and PBRM1. GO enrichment analysis revealed gene expression changes related to cell proliferation and extracellular matrix. Conclusions: Platelet count is a simple, non-invasive, and independent prognostic marker for ccRCC. This study supports the clinical utility of platelet count in risk stratification, offering the potential for integrating it into personalized treatment strategies. By predicting patient outcomes, platelet count can significantly improve clinical decision-making and guide therapeutic interventions for ccRCC patients.