Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2025; 31(26): 108662
Published online Jul 14, 2025. doi: 10.3748/wjg.v31.i26.108662
Histone deacetylases 10 as a prognostic biomarker correlates with tumor microenvironment and therapy response in colorectal cancer
Hai-Hang Nie, Xue-Ying Yang, Jing-Kai Zhou, Gui-Lin Gao, Lu Ding, Yun-Tian Hong, Ya-Li Yu, Pei-Shan Qiu, Zi-Yue Zeng, Jun Lai, Ting Zheng, Hai-Zhou Wang, Qiu Zhao, Fan Wang
Hai-Hang Nie, Jing-Kai Zhou, Yun-Tian Hong, Ya-Li Yu, Pei-Shan Qiu, Hai-Zhou Wang, Qiu Zhao, Fan Wang, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Hai-Hang Nie, Jing-Kai Zhou, Yun-Tian Hong, Ya-Li Yu, Pei-Shan Qiu, Hai-Zhou Wang, Qiu Zhao, Fan Wang, Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Wuhan 430071, Hubei Province, China
Hai-Hang Nie, Jing-Kai Zhou, Yun-Tian Hong, Ya-Li Yu, Pei-Shan Qiu, Hai-Zhou Wang, Qiu Zhao, Fan Wang, Hubei Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Xue-Ying Yang, Department of Medical Records, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, Hubei Province, China
Gui-Lin Gao, Department of Oral Diagnosis and Treatment Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, Hubei Province, China
Lu Ding, Department of Office of Academic Research, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Zi-Yue Zeng, Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Jun Lai, The Infirmary of Hangzhou Power Supply Company of State Grid, Zhejiang Electric Power Co., Ltd. Hangzhou 310020, Zhejiang Province, China
Ting Zheng, Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Co-first authors: Hai-Hang Nie and Xue-Ying Yang.
Co-corresponding authors: Fan Wang and Qiu Zhao.
Author contributions: Nie HH collected all public datasets and was responsible for the main analysis, then wrote this original draft; Gao GL and Yang XY completed immunohistochemistry, quantitative real-time PCR, western blotting; Zhou JK reviewed and edited this original draft; Yu YL was responsible for prognosis, tumor microenvironment analysis and data integration; Ding L and Hong YT was responsible for the collection of colorectal cancer tissues; Qiu PS and Zeng ZY conducted the construction of cell models, cell counting kit-8 assay, and colony formation assay, and wound healing assay; Zheng T, Wang HZ and Zhao Q were responsible for funding acquisition, supervision of the study; Wang F was the lead author of the study and guided selection of analysis. All authors have read and approved the final manuscript. All authors contributed to the study conception and design. All authors read and approved the final manuscript. Nie HH and Yang XY contributed equally to this work as co-first authors. Wang F is the principal investigator of this study and the principal investigator of the China National Natural Science Foundation project. He was responsible for the initial preliminary experiments, experimental design, and paper revision and review for this project. Zhao Q is the primary participant in the funding support for this study and the principal investigator for the later design adjustments, including the acquisition and analysis of tissue chips and the design of cell experiments.
Supported by National Natural Science Foundation of China, No. 82403279 and No. 82303181.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of the Zhongnan Hospital of Wuhan University Institutional Review Board [(Approval No. 2025001K]).
Informed consent statement: This study has obtained informed consent from all patients. All the methods were carried out in accordance with the relevant guidelines under the ethical approval and consent to participate section.
Institutional animal care and use committee statement: Our present study does not involve any animal experiments.
Conflict-of-interest statement: The authors in this articles have no relevant financial or non-financial interests to disclose.
Data sharing statement: All public datasets enrolled in this study could download from GEO database (https://www.ncbi.nlm.nih.gov/geo/) and the TCGA database (https://www.cancer.gov/ccg/research/genome-sequencing/tcga). All data generated or analyzed during this study are included in the supplementary information files of this article. Participants gave informed consent for data sharing.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fan Wang, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan 430071, Hubei Province, China. 2020283030092@whu.edu.cn
Received: April 21, 2025
Revised: May 18, 2025
Accepted: June 12, 2025
Published online: July 14, 2025
Processing time: 82 Days and 15 Hours
Abstract
BACKGROUND

The histone deacetylases 10 (HDAC10) is a HDAC family member, yet its importance in the context of colorectal cancer (CRC) development remains incompletely understood. The present study was thus developed to explore the mechanistic importance of HDAC10 as a regulator of CRC.

AIM

To investigate the impact of HDAC10 on tumor growth and its regulation in tumor microenvironment (TME) in CRC, we conducted this study.

METHODS

The study evaluated HDAC10 expression using immunohistochemistry analyses and assessed its prognostic value in CRC patients. HDAC10 depletion CRC cell lines were generated, and its biological functions were assessed through cell counting kit-8, wound healing, and colony formation assays. Furthermore, gene set variation analysis (GSVA) was employed to explore the potential molecular mechanisms of HDAC10 in CRC. The impact of HDAC10 on TME was subsequently assessed. Finally, the study investigated the influence of HDAC10 on the response to immunotherapy and chemotherapeutic drugs in CRC.

RESULTS

HDAC10 expression was significantly elevated in CRC and correlated with poor prognosis in patients. Knockdown of HDAC10 reduced colon cancer cell proliferation and migration capabilities. GSVA revealed a strong association between high HDAC10 expression and immune suppression. Additionally, high HDAC10 levels were correlated with a non-inflamed TME. Finally, patients with high HDAC10 expression showed reduced sensitivity to immunotherapy.

CONCLUSION

This study revealed the significance of HDAC10 in TME, therapy efficacy, and clinical prognosis in CRC, offering novel insights for therapeutic advancements in CRC.

Keywords: Histone deacetylases 10; Colorectal cancer; Tumor microenvironment; Immunotherapy; Prognosis

Core Tip: Histone deacetylases 10 (HDAC10), a HDAC family member, was overexpressed in colorectal cancer (CRC) and associated with poor prognosis. HDAC10 depletion inhibited CRC cell proliferation and migration, suggesting its oncogenic role. Gene set variation analysis linked elevated HDAC10 expression to immunosuppressive pathways and a non-inflamed tumor microenvironment (TME), characterized by reduced immune cell infiltration. CRC patients with high HDAC10 levels showed reduced sensitivity to immunotherapy, indicating therapeutic resistance. Our findings highlight HDAC10’s critical role in shaping the TME, treatment response, and clinical outcomes in CRC, supporting its potential as a therapeutic target to improve CRC management.