Development and Validation of an IL6/JAK/STAT3-Related Gene Signature to Predict Overall Survival in Clear Cell Renal Cell Carcinoma

Background: Traditional clinicopathological features (TNM, pathology grade) are often insufficient in predictive prognosis accuracy of clear cell renal cell carcinoma (ccRCC). The IL6-JAK-STAT3 pathway is aberrantly hyperactivated in many cancer types, and such hyperactivation is generally associated with a poor clinical prognosis implying that it can be used as a promising prognosis indicator. The relation between the IL6-JAK-STAT3 pathway and ccRCC remains unknown. Methods: We evaluated the levels of various cancer hallmarks and filtered out the promising risk hallmarks in ccRCC. Subsequently, a prognosis model based on these hallmark-related genes was established via weighted correlation network analysis and Cox regression analysis. Besides, we constructed a nomogram based on the previous model with traditional clinicopathological features to improve the predictive power and accuracy. Results: The IL6-JAK-STAT3 pathway was identified as the promising risk hallmarks in ccRCC, and the pathway-related prognosis model based on five genes was built. Also, the nomogram we developed demonstrated the strongest and most stable survival predictive ability. Conclusion: Our study would provide new insights for guiding individualized treatment of ccRCC patients.