Development and Validation of a Necroptosis-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

Necroptosis is a form of cell death, this study aimed to explore and verify the relationship between clear cell renal cell carcinoma and necroptosis, and to construct a necroptosis-related prognostic signature for diagnosis and treatment of clear cell renal cell carcinoma. 159 necroptosis-related genes were screened from the Kyoto encyclopedia of genes and genomes database of which 51 were differentially expressed in clear cell renal cell carcinoma, which included 16 prognosis-associated genes. Enrichment analysis showed that most of the 16 genes were related to necroptosis, autophagy and the Wingless-related integration site signaling pathway. From the 16 genes, 11 independent necroptosis-related genes associated with clear cell renal cell carcinoma prognosis were screened by least absolute shrinkage and selection operator regression and multivariate Cox regression. These genes (BH3 interacting domain death agonist, Janus kinase 3, RANBP2-type and C3HC4-type zinc finger containing 1, solute carrier family 25 member 4, interferon gamma receptor 2, phospholipase A2 group IVD, toll-like receptor 3, H2A clustered histone 7, interferon regulatory factor 9, phospholipase A2 group IVB and H2A clustered histone 17) were used to construct a prognostic signature which was assessed by multivariate Cox regression analysis. Also, the relationship between the risk score and the stage and grade was determined. Receiver operating characteristic analysis and the decision curve analysis demonstrated the validity and clinical value of the prediction model which was internally validated. In this study, we explored the potential link between clear cell renal cell carcinoma and necroptosis to establish and validate an 11 gene prognostic signature that can effectively predict clear cell renal cell carcinoma prognosis.