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组蛋白去乙酰化酶10作为一种预后生物标志物与结直肠癌的肿瘤微环境及治疗反应相关。

Histone deacetylases 10 as a prognostic biomarker correlates with tumor microenvironment and therapy response in colorectal cancer.

作者信息

Nie Hai-Hang, Yang Xue-Ying, Zhou Jing-Kai, Gao Gui-Lin, Ding Lu, Hong Yun-Tian, Yu Ya-Li, Qiu Pei-Shan, Zeng Zi-Yue, Lai Jun, Zheng Ting, Wang Hai-Zhou, Zhao Qiu, Wang Fan

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China.

Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Wuhan 430071, Hubei Province, China.

出版信息

World J Gastroenterol. 2025 Jul 14;31(26):108662. doi: 10.3748/wjg.v31.i26.108662.

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.

摘要

背景

组蛋白去乙酰化酶10(HDAC10)是组蛋白去乙酰化酶家族成员,但其在结直肠癌(CRC)发生发展过程中的重要性仍未完全明确。因此,本研究旨在探讨HDAC10作为CRC调节因子的机制重要性。

目的

为了研究HDAC10对CRC肿瘤生长的影响及其在肿瘤微环境(TME)中的调节作用,我们开展了本研究。

方法

本研究采用免疫组织化学分析评估HDAC10表达,并评估其在CRC患者中的预后价值。构建HDAC10缺失的CRC细胞系,通过细胞计数试剂盒-8、伤口愈合和集落形成试验评估其生物学功能。此外,采用基因集变异分析(GSVA)探讨HDAC10在CRC中的潜在分子机制。随后评估HDAC10对TME的影响。最后,本研究调查了HDAC10对CRC免疫治疗和化疗药物反应的影响。

结果

HDAC10在CRC中的表达显著升高,且与患者预后不良相关。敲低HDAC10可降低结肠癌细胞的增殖和迁移能力。GSVA显示HDAC10高表达与免疫抑制密切相关。此外,HDAC10高表达水平与非炎症性TME相关。最后,HDAC10高表达的患者对免疫治疗的敏感性降低。

结论

本研究揭示了HDAC10在CRC的TME、治疗疗效和临床预后中的重要性,为CRC治疗进展提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bae/12264853/6041386340df/wjg-31-26-108662-g001.jpg

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