Taylor & Francis Group
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Multimolecular characteristics of cell-death related hub genes in human cancers: a comprehensive pan-cancer analysis

posted on 2022-11-07, 21:40 authored by Dingtao Hu, Tingyu Zhang, Ziye Yan, Linlin Wang, Yuhua Wang, Nana Meng, Bizhi Tu, Ying Teng, Zhen Li, Xiaoqi Lou, Yu Lei, Xiaoshuang Ren, Yanfeng Zou, Fang Wang

Failure of the normal process of cell death pathways contributes to the defection of immune systems and the occurrence of cancers. The key genes, the multimolecular mechanisms, and the immune functions of these genes in pan-cancers remain unclear. Using online databases of The Cancer Genome Atlas, GEPIA2, TISIDB, HPA, Kaplan-Meier Plotter, PrognoScan, cBioPortal, GSCALite, TIMER, and Sangerbox, we identified the key genes from the six primary cell death-related pathways and performed a comprehensive analysis to investigate the multimolecular characteristics and immunological functions of the hub genes in 33 human cancers. We identified five hub genes in the six primary cell death-related pathways (JUN, NFKB1, CASP3, PARP1, and TP53). We found that CASP3, PARP1, and TP53 were overexpressed in 28, 23, and 27 cancers. The expression of the five genes was associated with the development and prognosis of many cancers. Particularly, JUN, NFKB1, CASP3, and TP53 have prognostic values in Brain Lower Grade Glioma (LGG), while PARP1 and CASP3 could predict the survival outcomes in Adrenocortical carcinoma (ACC). In addition, an extensive association between five genes’ expression, DNA methylation, and tumor-immune system interactions was noticed. The five cell death-related hub genes could function as potential biomarkers for various cancers, particularly LGG and ACC. The immunological function analysis of the five genes also proposes new targets for developing immunosuppressants and improving the immunotherapy efficacy of cancers. However, further extensive clinical and experimental research are required to validate their clinical values.


This work was supported by the grant from the National Natural Science Foundation of China (grant numbers 81602115), the Foundation of Supporting Program for theExcellent Young Faculties in University of Anhui Province in China (gxyq2019012), grants for Scientific Research of BSKY from the First Affiliated Hospital of Anhui Medical University. and grants for Outstanding Youth from the First Affiliated Hospital of Anhui Medical University; Foundation of Supporting Program for the Excellent Young Faculties in University of Anhui Province in China