A cellular senescence-related signature for predicting prognosis, immunotherapy response, and candidate drugs in patients treated with transarterial chemoembolization (TACE)

**Background:** Cellular senescence plays a critical role in the development, progression, and remodeling of the tumor microenvironment (TME). However, limited research has focused on cellular senescence in hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). Understanding the relationship between cellular senescence, post-TACE prognosis, the TME, and responses to immunotherapy is essential.

**Methods:** We analyzed the GSE104580 dataset to identify differentially expressed genes (DEGs). A cellular senescence-related signature was developed using LASSO Cox regression on the GSE14520 dataset and validated in the ICGC dataset. We compared high- and low-risk subgroups using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Correlation analyses were performed to examine the associations between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity.

**Results:** We developed and validated a cellular senescence-related signature that includes FOXM1, CDK1, CHEK1, and SERPINE1. Patients in the high-risk group had significantly lower overall survival (OS) compared to those in the low-risk group. The high-risk group exhibited activated carcinogenic pathways, increased infiltration of immunosuppressive cells, and overexpression of immunomodulatory genes. These patients also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053, with potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L.

**Conclusions:** This study developed a cellular senescence-related signature that can predict the prognosis and treatment response of HCC patients after TACE, providing a foundation for personalized treatment strategies.