ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1543419
Pan-cancer analysis reveals TRA16 as a master regulator of human carcinogenesis
Provisionally accepted
- 1Henan Provincial People's Hospital, Zhengzhou, Henan Province, China
- 2Peking Union Medical College Hospital (CAMS), Beijing, Beijing Municipality, China
- 3Intelliphecy Center for Systems Medicine, Shenzhen, China
- 4Yantian District People's Hospital, Shenzhen, Guangdong Province, China
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The nuclear receptor TR4 binding protein, TRA16, has been implicated in lung carcinogenesis; however, its broader role in cancer remains largely unexplored.Here, we present a comprehensive pan-cancer analysis of TRA16 across human malignancies. Correlation analysis identified the cell cycle as the top enriched pathway among TRA16-associated genes, with key transcription factors, including RB-E2F, MYC, and TP53, regulating genes co-expressed with TRA16. In liver cancer organoid models, TRA16 and its associated genes were significantly upregulated. Intercellular communication analysis further revealed that TRA16positive cells exhibited enhanced autocrine signaling and increased overall signaling activity. Notably, patients with high TRA16 expression demonstrated an elevated tumor mutation burden (TMB) in both TP53-dependent and TP53-independent manners. These findings suggest that TRA16 may function as a master regulator in human cancers, contributing to tumor progression through multiple oncogenic pathways.s
Keywords: oncogene, nuclear receptor, single cell, Systems Medicine, Pan-cancer analysis
Received: 11 Dec 2024; Accepted: 16 Apr 2025.
Copyright: © 2025 Zhu, Gao, Huang, Chen, Wang, Wu, Sun and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyun Huang, Intelliphecy Center for Systems Medicine, Shenzhen, China
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