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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Translational Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1418456
This article is part of the Research Topic Molecular Targets in Oncological and Hematological Disease Management: Innovations in Precision Medicine View all 7 articles

Pan-cancer analyses reveal the molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target

Provisionally accepted
Yan C. ZHANG Yan C. ZHANG 1Jie Zheng Jie Zheng 1Jin Liu Jin Liu 2Yanxia Li Yanxia Li 1Guo Q. Xing Guo Q. Xing 1Shu P. Zhang Shu P. Zhang 1Hekai Chen Hekai Chen 1Jian Wang Jian Wang 1Jiang Z. Shao Jiang Z. Shao 1Yuan Y. Li Yuan Y. Li 1Min Z. JIANG Min Z. JIANG 1Zi Y. Pan Zi Y. Pan 3Xiaozhi Liu Xiaozhi Liu 1Ping Xu Ping Xu 1*Han W. WU Han W. WU 3*
  • 1 Tianjin Fifth Central Hospital, Tianjin, China
  • 2 North China University of Science and Technology, Tangshan, Hebei Province, China
  • 3 First Hospital, Peking University, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of single nucleotide variations (SNVs) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variations (CNVs) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.

    Keywords: TET family genes, Pan-cancer analysis, Tumor Microenvironment, drug sensitivity, Therapeutic target

    Received: 16 Apr 2024; Accepted: 28 May 2024.

    Copyright: © 2024 ZHANG, Zheng, Liu, Li, Xing, Zhang, Chen, Wang, Shao, Li, JIANG, Pan, Liu, Xu and WU. 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:
    Ping Xu, Tianjin Fifth Central Hospital, Tianjin, China
    Han W. WU, First Hospital, Peking University, Beijing, Beijing Municipality, China

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