1. A cellular senescence-related signature for predicting prognosis, immunotherapy response, and candidate drugs in patients treated with transarterial chemoembolization (TACE)
- Author
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Ning He, Wenjing Zhao, Wenlong Tian, Ying Wu, Jian Xu, Yunyan Lu, Xudong Chen, and Hui Zhao
- Subjects
Hepatocellular carcinoma ,Transcatheter arterial chemoembolization ,Cellular senescence ,Prognosis ,Tumor immune microenvironment ,Immunotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Cellular senescence is essential to TME development, progression, and remodeling. Few studies have examined cellular senescence in HCC after TACE. Investigating the relationship between cellular senescence, post-TACE prognosis, the TME, and immune treatment responses is crucial. Methods We analyzed the GSE104580 dataset to identify DEGs. A cellular senescence-related signature was developed using LASSO Cox regression in the GSE14520 dataset and validated in the ICGC dataset. High- and low-risk subgroups were compared using GSVA and GSEA. Correlation studies were conducted to explore the relationship between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity. Results A cellular senescence-related signature comprising FOXM1, CDK1, CHEK1, and SERPINE1 was created and validated. High-risk patients showed significantly lower OS than low-risk patients. High-risk patients had carcinogenetic pathways activated, immunosuppressive cells infiltrated, and immunomodulatory genes overexpressed. They also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053 and potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L. Conclusions This study constructed a cellular senescence-related signature that could be used to predict HCC patients’ responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans.
- Published
- 2024
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