全面分析N6-甲基腺苷(m6A)RNA甲基化调控因子和肿瘤微环境细胞浸润对胃食管腺癌预后和免疫治疗的影响

IF 2.7 4区 医学 Q2 Medicine Canadian Journal of Gastroenterology and Hepatology Pub Date : 2022-11-21 eCollection Date: 2022-01-01 DOI:10.1155/2022/3506518
Duanrui Liu, Mingjie Yuan, Zongming Wang, Liping Sun, Yusong Fang, Xiaoli Ma, Lulu Zhang, Yuanxin Xing, Jingyu Zhu, Yunyun Liu, Wenshuai Zhu, Shuqin Bao, Yanfei Jia, Yunshan Wang
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引用次数: 0

摘要

研究目的胃食管腺癌(GEA)是一种高致死率的异质性癌症。RNA N6-甲基腺苷(m6A)修饰在塑造个体肿瘤微环境(TME)特征方面发挥着不可忽视的作用。然而,在 GEA 中,m6A 修饰模式和 TME 细胞浸润特征的分布和关系仍然未知:在这项研究中,我们通过评估RNA测序数据,重点研究了公共数据库中不同的m6A修饰模式,从而研究了GEA的TME。我们评估了m6A修饰的内在模式与临床病理特征、潜在生物通路、肿瘤免疫细胞浸润、肿瘤学结果和治疗反应之间的关联。通过 qRT-PCR 分析验证了关键 m6A 调节因子和模块基因的表达:结果:我们发现了两种不同的GEA m6A修饰模式(1/2亚群),并将两个亚群与TME细胞浸润特征相关联。簇2亚组与较差的预后、下调的PD-1表达、较高的风险评分和独特的免疫细胞浸润相关。此外,通过整合 PPI 和 WGCNA 网络分析,确定了与 GEA 免疫浸润密切相关的关键模块基因,从而找到免疫治疗标记物。棕色模块中的COL4A1和COL5A2与GEA患者的预后、PD-1/L1和CTLA-4表达显著相关。最后,利用m6A调节因子相关特征构建了一个预后风险评分,该评分代表了GEA的一个独立预后因素。有趣的是,COL5A2的表达与抗PD-1免疫疗法的反应、m6A调节因子的表达和风险评分有关:我们的研究发现,m6A RNA甲基化调节因子是GEA恶性进展过程中的一类重要参与者,与TME的复杂性有关。COL5A2可能是预测抗PD-1免疫疗法反应和患者预后的潜在生物标志物。
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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Comprehensive Analysis of N6-Methyladenosine (m6A) RNA Methylation Regulators and Tumour Microenvironment Cell Infiltration Involving Prognosis and Immunotherapy in Gastroesophageal Adenocarcinomas.

Objective: Gastroesophageal adenocarcinoma (GEA) is a high deadly and heterogeneous cancer. RNA N6-methyladenosine (m6A) modification plays a non-negligible role in shaping individual tumour microenvironment (TME) characterizations. However, the landscape and relationship of m6A modification patterns and TME cell infiltration features remain unknown in GEA.

Methods: In this study, we examined the TME of GEA using assessments of the RNA-sequencing data focusing on the distinct m6A modification patterns from the public databases. Intrinsic patterns of m6A modification were evaluated for associations with clinicopathological characteristics, underlying biological pathways, tumour immune cell infiltration, oncological outcomes, and treatment responses. The expression of key m6A regulators and module genes was validated by qRT-PCR analysis.

Results: We identified two distinct m6A modification patterns of GEA (cluster 1/2 subgroup), and correlated two subgroups with TME cell-infiltrating characteristics. Cluster 2 subgroup correlates with a poorer prognosis, downregulated PD-1 expression, higher risk scores, and distinct immune cell infiltration. In addition, PPI and WGCNA network analysis were integrated to identify key module genes closely related to immune infiltration of GEA to find immunotherapy markers. COL4A1 and COL5A2 in the brown module were significantly correlated to the prognosis, PD-1/L1 and CTLA-4 expression of GEA patients. Finally, a prognostic risk score was constructed using m6A regulator-associated signatures that represented an independent prognosis factor for GEA. Interestingly, COL5A2 expression was linked to the response to anti-PD-1 immunotherapy, m6A regulator expression, and risk score.

Conclusion: Our work identified m6A RNA methylation regulators as an important class of players in the malignant progression of GEA and were associated with the complexity of the TME. COL5A2 may be the potential biomarker which contributes to predicting the response to anti-PD-1 immunotherapy and patients' prognosis.

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来源期刊
CiteScore
4.80
自引率
0.00%
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0
审稿时长
37 weeks
期刊介绍: Canadian Journal of Gastroenterology and Hepatology is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of gastroenterology and liver disease - medicine and surgery. The Canadian Journal of Gastroenterology and Hepatology is sponsored by the Canadian Association of Gastroenterology and the Canadian Association for the Study of the Liver.
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