DNA hypomethylation of INHBA promotes tumor progression and predicts prognosis and immune status of gastric cancer.

IF 2.7 3区生物学

Hereditas Pub Date : 2024-11-14 DOI:10.1186/s41065-024-00347-7

Xueying Li, Haizhong Jiang, Yangbo Fu, Qiying Hu, Xianlei Cai, Guoqiang Xu

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引用次数: 0

Abstract

Objective: Gastric cancer (GC) is characterized by its high malignancy and poor prognosis. However, the role of Inhibin subunit beta A (INHBA) in GC remains insufficiently understood. This study aims to comprehensively evaluate the clinical significance, biological roles, and possible mechanisms of INHBA in GC.

Methods: Expression levels and survival analyses of the Inhibin beta family were assessed using online databases. A prediction model based on INHBA was developed. In addition, the associations between INHBA expression and immune status, and chemotherapy sensitivity were explored. In vitro experiments were conducted to investigate the biological impact of INHBA on GC cells. Pyrosequencing and the DNA methylation inhibitor, 5-AZA-2'-deoxycytidine (5-AZA-dC) were employed to elucidate the mechanisms underlying INHBA function.

Results: Our findings revealed that INHBA exhibited high expression in GC patients, and elevated INHBA expression correlated with worse outcomes. We developed a novel nomogram incorporating INHBA, age, and tumor node metastasis (TNM) stage to predict the prognosis of GC patients. Additionally, INHBA was found to be associated with suppressed infiltration of immune cells and chemosensitivity. Functionally, INHBA promoted the proliferation and invasiveness of GC cells. Mechanistically, pyrosequencing revealed DNA Hypomethylation of INHBA in the first exon region, and the effects of INHBA silencing were rescued by 5-AZA-dC treatment.

Conclusion: Our study suggests that DNA hypomethylation of INHBA contributes to the progression of GC. Furthermore, INHBA holds promise as a valuable biomarker for prognostic evaluation and immune status prediction in GC patients.

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INHBA的DNA低甲基化促进肿瘤进展，并预测胃癌的预后和免疫状态。

目的：胃癌（GC）的特点是恶性程度高、预后差。然而，人们对抑制素亚基 beta A（INHBA）在胃癌中的作用仍不够了解。本研究旨在全面评估 INHBA 在 GC 中的临床意义、生物学作用和可能机制：方法：使用在线数据库评估抑制素 beta 家族的表达水平和生存分析。方法：利用在线数据库对抑制素 beta 家族的表达水平和生存分析进行评估，并建立了基于 INHBA 的预测模型。此外，还探讨了INHBA表达与免疫状态和化疗敏感性之间的关联。体外实验研究了 INHBA 对 GC 细胞的生物学影响。采用热测序和DNA甲基化抑制剂5-AZA-2'-脱氧胞苷（5-AZA-dC）来阐明INHBA的功能机制：结果：我们的研究结果表明，INHBA在GC患者中高表达，INHBA表达升高与预后恶化相关。我们开发了一种新的提名图，结合 INHBA、年龄和肿瘤结节转移（TNM）分期来预测 GC 患者的预后。此外，我们还发现 INHBA 与免疫细胞浸润抑制和化疗敏感性有关。在功能上，INHBA 能促进 GC 细胞的增殖和侵袭性。从机理上讲，热释光测序发现INHBA的第一个外显子区存在DNA低甲基化，5-AZA-dC处理可挽救INHBA沉默的影响：我们的研究表明，INHBA的DNA低甲基化是导致GC进展的原因之一。此外，INHBA有望成为一种有价值的生物标记物，用于GC患者的预后评估和免疫状态预测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.