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

作者：Biao Gao, Yafei Wang, Shichun Lu · 发表于：Scientific Reports · 年份：2023 · DOI：10.1038/s41598-023-28436-z · 被引用次数：11 · 研究领域：Immune cells in cancer、Telomeres, Telomerase, and Senescence、Single-cell and spatial transcriptomics

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 prognost...