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

组蛋白去乙酰化酶 10 作为预后生物标志物与结直肠癌的肿瘤微环境和治疗反应相关

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作者: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
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.

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