Cellular senescence affects energy metabolism, immune infiltration and immunotherapeutic response in hepatocellular carcinoma

Abstract

Aging is an inevitable consequence of life, characterized by a progressive decline in tissue and organ function and an increased risk of death. There is growing evidence that aging is closely related to tumor development and immune regulation. However, in hepatocellular carcinoma, the relationship between cellular senescence and immune infiltration, energy metabolism, chemokines, and immunotherapeutic response is unclear and needs further study. We first analyzed 274 cellular senescence-associated genes by the NMF algorithm and identified two cellular senescence-associated clusters. Subsequently, we compared the differences between the two clusters, in terms of immune infiltration, energy metabolism, chemokines, and immunotherapeutic response to treatment. We further constructed risk models using cellular senescence-associated signature genes that could effectively identify the two subpopulations. Finally, we validated the validity and robustness of the risk model using an external dataset. We found significant differences in survival prognosis between two cellular senescence-associated clusters. In addition, we found significant differences in immune cell infiltration, expression of energy metabolism-related genes, expression of chemokine-related genes, expression of immune checkpoint-related genes, Tumor Immune Dysfunction and Exclusion between the two clusters. Also, a scoring system associated with cellular senescence was developed and validated as an independent prognostic indicator. It was validated as an independent prognostic factor and immunotherapeutic predictor for HCC. It was validated as an independent prognostic factor and immunotherapeutic predictor for HCC. The cellular senescence-related scoring system was validated as an independent prognostic factor and immunotherapy predictor for HCC, and patients with low CSS were characterized by prolonged survival time. Our study confirmed the relationship between cellular senescence and immune cell infiltration, energy metabolism, chemokines, expression of immune checkpoint-related genes, and response to immunotherapy. This enhances our understanding of cellular senescence and tumor immune microenvironment, energy metabolism, chemokines, and provides new insights to improve immunotherapy outcomes in HCC patients. It provides new insights to improve the outcome of immunotherapy in HCC patients.

Identification and functional analysis of lactic acid metabolism-related differentially expressed genes in hepatocellular carcinoma

“…The incorporation or reduction of molecular oxygen and powerful antioxidant activity play a key role in HCC treatment ( Ahmed et al, 2018 ; Kim et al, 2022 ). In addition, cellular senescence affects immune infiltration and immunotherapeutic responses in HCC ( Gao et al, 2023 ). The activation of the P53 signaling pathway is involved in HCC carcinogenesis, and inhibition of P53 can improve the therapies response in HCC ( Krstic et al, 2022 ).…”

Identification of common hub genes in gastrointestinal cancers and their role in prognosis and Immune cell infiltration in hepatocellular carcinoma

“…Currently, studies on prognostic models related to HCC, such as copper death and cell senescence, have been successively conducted [31,32]. The current study selected three genes among the 10 CHG genes to successfully construct a prognostic model of HCC.…”