Comprehensive Pan-Cancer Analysis of Senescence With Cancer Prognosis and Immunotherapy

Abstract

Senescence is a double-edged sword in tumorigenesis and affects the immunotherapy response through the modulation of the host’s immune system. However, there is currently a lack of comprehensive analysis of the senescence-related genes (SRGs) in human cancers, and the predictive role of senescence in cancer immunotherapy response has not been explored. The multi-omics approaches were performed in this article to conduct a systematic pan-cancer genomic analysis of SRGs in cancer. In addition, we calculated the generic senescence score (SS) to quantify the senescence levels in cancers and explored the correlations of SS with cancer prognosis, biological processes, and tumor microenvironment (TME). The gene signatures were deregulated in multiple cancers and indicated a context-dependent correlation with prognosis, tumor-immune evasion, and response to therapy across various tumor types. Further analysis disclosed that SS was positively associated with the infiltration levels of immune suppressive cells, including induced Tregs (iTregs), central memory Ts (Tcms), and natural Tregs (nTregs), and negatively associated with immune killer cells, including natural killers (NKs) and mucosal-associated invariant Ts (MAITs). Moreover, the SS was significantly correlated with tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), immune-related genes, and immune checkpoints and had a predictive value of immunotherapy response. Thus, the expression of SRGs was involved in resistance to several anticancer drugs. Our work illustrates the characterization of senescence across various malignancies and highlights the potential of senescence as a biomarker of the response to immunotherapy.

Exploring the role of cellular senescence in cancer prognosis across multiple tumor types

“…Zhao et al. obtained sequencing and clinical information datasets for tumor and normal tissues from the TCGA and the Genotype-Tissue Expression (GTEx) ( 35 ). With the help of ssGSEA, they also obtained their senescence score.…”

A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer

“…The proposal of senescence-related genomes provide data support for further research on the relationship between senescence and tumors. Using senescence-related datasets from the literature, a comprehensive pancancer analysis was conducted (Zhao et al, 2022). The results showed that senescence-related genes are widely different in different cancers and that cell senescence has an important impact on the tumor immune microenvironment.…”