Research Paper Volume 14, Issue 2 pp 961—974
Integrative bioinformatics and experimental analysis revealed TEAD as novel prognostic target for hepatocellular carcinoma and its roles in ferroptosis regulation
- 1 Center for Molecular Medicine, Xiangya Hospital, Key Laboratory of Molecular Radiation Oncology of Hunan Province, Central South University, Changsha 410008, Hunan, China
- 2 Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
- 3 Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
- 4 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
- 5 Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
- 6 Department of Emergency, Xiangya Changde Hospital, Changde 415000, Hunan, China
- 7 Department of Pathology, Xiangya Changde Hospital, Changde 415000, Hunan, China
- 8 Department of Burn and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
Received: November 22, 2021 Accepted: January 17, 2022 Published: January 25, 2022https://doi.org/10.18632/aging.203853
How to Cite
Copyright: © 2022 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Transcriptional enhanced associate domain (TEAD) family consists of four members TEAD1/2/3/4 that regulate cell growth, stem cell functions and organ development. As the downstream of Hippo signaling pathway, TEAD family is involved in the progression of several cancers. However, the precise biology functions of TEAD family in hepatocellular carcinoma (HCC) have not been reported yet.
Methods: We apply bioinformatics analysis based on databases including UALCAN, Oncomine, GEPIA, Kaplan-Meier plotter, WebGestalt, cBioPortal, TIMER2.0, and in vitro experimental evidence to identify the exact roles of TEAD family in HCC.
Results: The results indicated that TEAD2/4 were significantly upregulated in HCC compared with normal tissues. Downregulated of TEAD2 could promote the death of HCC cells through inducing ferroptosis by iron accumulation and subsequent oxidative damage. According to the Kaplan-Meier plotter database, we found that the high expression of TEAD2 was significantly associated with poor disease-specific survival, overall survival, progression-free survival and relapse-free survival. In aspect of cancer immunity, Tumor Immune Estimation Resource algorithm showed that the expression of TEAD family members was obviously related to multiple of infiltrating immune cells including macrophages, neutrophils, dendritic cells, B cells, CD8+ T cells and CD4+ T cells. Finally, we conducted the functional enrichment analysis including protein-protein interaction network, gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway based on the TEAD family-associated coexpression genes.
Conclusion: The study provided deep insight information of TEAD family in the diagnostic and prognostic evaluation of HCC patients.