Development and validation of Cellular Senescence-Related Gene Signature for predicting the survival and immunotherapeutic responses in Skin Cutaneous Melanoma

Abstract

Background Accumulating evidence has suggested the impact of cellular senescence on tumorigenesis, development, and immune modulation in cancers. However, the prognostic value of cellular senescence-related genes (SRGs) and their association with immunotherapy response remain unexplored in skin cutaneous melanoma (SKCM) patients. Methods In this study, we explored the expression profiles of 279 SRGs in 469 SKCM patients included from TCGA database. The univariate and least absolute shrinkage and selection operator (LASSO) were conducted to construct a cellular senescence-related signature (SRS), and Kaplan–Meier survival curves as well as ROC curve were used to validate the predictive capability. The GSE65904 dataset was further used to validate the predictive ability of prognostic signature. Moreover, we explored the correlations of the SRS with tumor-infiltrating immune cells and response to immunotherapy. The expression levels of prognosis related SRGs were validated based on immunohistochemistry. In addition, consensus clustering analysis was performed to stratify SKCM patients into different clusters and compared them in OS. Results We developed a prognostic prediction SRS for patients with SKCM and verified patients in low-risk group were associated with better prognosis. Moreover, the correlation analysis showed that the SRS could predict the infiltration of immune cells and immune status of the immune microenvironment in SKCM, and patients with low-risk score might benefit from immunotherapy. In addition, all the SKCM patients in this study were classified into three clusters based on the mRNA expression profiles of 113 SRGs, which revealed that cluster 1 suffered poorer outcomes relative to clusters 2 and 3. Conclusions The SRS developed in this study could be used as a prediction tool in survival assessment and immunotherapy for SKCM patients.