ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1667589
This article is part of the Research TopicInnovative Strategies for the Discovery of New Therapeutic Targets in Cancer TreatmentView all 7 articles
CLIC6's role in cancer: from broad analysis to breast cancer validation
Provisionally accepted
Junyi Wang1
Yiyang Wang1Haotian Ma1
Yongxiang Li1Jiayue Hou2Jiaqi Li2
Dilimulati Ismtula1*
Chenming Guo1*- 1First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- 2Xinjiang Medical University, Urumqi, China
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Background Chloride Intracellular Channel 6 (CLIC6) is a potential cancer therapy target due to its close association with tumor development. However, its diagnostic and prognostic roles, as well as its impact on immune regulation in different cancers, remain unclear. Methods This study utilized public databases like TCGA and GEO to analyze CLIC6 expression, diagnostic value, and prognostic significance across various cancers. It examined genetic and epigenetic variations, immune correlations, and performed functional enrichment analysis to uncover CLIC6-related pathways. Western blotting confirmed CLIC6 protein levels in breast cancer samples, while CCK-8, colony formation, transwell, and scratch assays evaluated its role in cell proliferation and migration. Tissue microarray and immunohistochemistry further validated CLIC6 expression in breast cancer. Results Research shows that CLIC6 expression is typically lower in most cancers compared to normal tissues, with distinct patterns across different stages. It serves as a useful diagnostic marker and potential prognostic factor for BRCA, LUAD, STAD, and LGG. CLIC6 mutations are common in many cancers and affect prognosis. In most tumors, CLIC6 expression correlates with m6A methylation, and its promoter is highly methylated. In BRCA, the expression of CLIC6 is related to bacterial defense, immune response, endopeptidase regulation, neuropeptide signaling, and amino acid transport. It is expressed at low levels in BRCA tissues, and we speculate that higher CLIC6 expression may be protective. Conclusion In conclusion, CLIC6 can serve as a key biomarker for various cancers, and its expression level is related to the tumor immune microenvironment and the outcomes in selected cancers, further validation is warranted. Our research on CLIC6 in BRCA has revealed new potential for tumor treatment strategies targeting this marker.
Keywords: CLIC6, Pan-cancer, diagnosis, prognosis, Methylation, tumor immunity
Received: 16 Jul 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 Wang, Wang, Ma, Li, Hou, Li, Ismtula and Guo. 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:
Dilimulati Ismtula, mlt0306@sina.com
Chenming Guo, gcm_xjmu@yeah.net
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