Comprehensive Analysis of Cellular Senescence-Related Genes in Prognosis, Molecular Characterization and Immunotherapy of Hepatocellular Carcinoma

Abstract

Background Cellular senescence is a tumor suppressive response in which the cell cycle is in a state of permanent arrest and can inhibit tumor cell proliferation. In recent years, induction of cellular senescence has been shown to be important for antitumor therapy, and the link between cellular senescence and clinical prognosis and immunotherapy of hepatocellular carcinoma is still unknown. Methods We performed enrichment analysis of genes in three cellular senescence gene sets, screened for gene sets significantly enriched in hepatocellular carcinoma and extracted genes from them. Signature were constructed using senescence-related genes, and their expression was verified at the protein and RNA levels. Survival, clinical staging and grading, immune infiltration, immunotherapy, and drug sensitivity were also analyzed between risk groups. Results The q-PCR and immunohistochemistry results revealed significant differences in the expression of the signature genes between normal and tumor tissues. Significant differences in clinicopathological features, prognosis and immune infiltration were observed between risk groups. In the low-risk group, better OS and lower TMB scores were demonstrated, while the high-risk group had higher immune checkpoint expression, as well as lower risk of immune escape. In addition, we found that the High-risk group was more sensitive to sorafenib. Conclusion In summary, the signature constructed using aging-related genes can reliably predict patient prognosis and immunotherapy efficacy, providing a new idea for immune system therapy of hepatocellular carcinoma.

Cellular Senescence in Liver Cancer: How Dying Cells Become “Zombie” Enemies

“…Overall, the realization of a prognostic model for cellular senescence risk score can not only be exploited to predict HCC patients' prognosis, but can also provide more strategies for the clinical treatment of HCC patients. Accordingly, recent studies reveal that senescencerelated gene signatures can also be used to predict the immunotherapy response [129]. However, further experiments and clinical data are needed to validate the involvement of the senescence mechanism in HCC progression and prognosis.…”