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胃癌中 m6A 相关 lncRNA 的肿瘤免疫浸润和免疫微环境分析及其预后意义。

Analysis and prognostic significance of tumour immune infiltrates and immune microenvironment of m6A-related lncRNAs in patients with gastric cancer.

机构信息

Department of General Surgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College (University), Nanchong, 637000, Sichuan, China.

Clinical Research Group, Grade 2017 in Department of Clinical Medicine, North Sichuan Medical College (University), Nanchong, 637000, Sichuan, China.

出版信息

BMC Med Genomics. 2022 Jul 25;15(1):164. doi: 10.1186/s12920-022-01318-5.

Abstract

BACKGROUND

Studies have shown that long noncoding RNAs and N6-methyladenosine play important roles in gastric cancer. The purpose of this study was to determine the correlation and prognostic value of m6A-related lncRNAs and immune infiltration in gastric cancer.

METHODS

We downloaded the clinically related information and RNA-Seq transcriptome data of gastric cancer patients from the TCGA database. Univariate Cox regression analysis and Pearson analysis were used to screen out m6A-related lncRNAs. Consensus cluster analysis was used to divide the sample into two clusters, and LASSO analysis and Cox regression analysis were used to construct a risk scoring model.

RESULTS

A total of 25 lncRNA expression profiles were screened, and gastric cancer patients were divided into different subtypes. Cluster 2 had a better prognosis, but its stromal score, ESTIMATE score and immune score were low. Cluster 1 was rich in resting memory CD4 T cells, regulatory T cells, monocytes, and resting mast cells, and Cluster 2 was rich in activated memory CD4 T cells and follicular helper T cells. Thirteen lncRNAs were selected to construct a risk model, and the prognosis of gastric cancer patients in the high-risk group was poor. The expression of PD-L1 in tumours is significantly higher than that in normal tissues. Univariate and multivariate Cox regression analysis results showed that the overall survival rate was significantly related to stage and the risk score, which can be used as an independent prognostic factor. The results of the heatmap and scatter plot showed that clusters (P = 0.0045) and grade (G1-2, G3, P = 0.0037) were significantly related to prognosis. The relationship between the risk score and immune cell infiltration showed that memory B cells, resting dendritic cells, M0 macrophages, and M2 macrophages were positively correlated with the risk score, while resting mast cells, monocytes, activated NK cells, and follicular helper T cells were negatively correlated with the risk score.

CONCLUSION

The results of this study indicate that m6A-related lncRNAs may play an important role in the prognosis of gastric cancer patients and the tumour immune microenvironment and may provide help for the treatment of gastric cancer patients.

摘要

背景

研究表明,长非编码 RNA 和 N6-甲基腺苷在胃癌中发挥重要作用。本研究旨在确定胃癌中 m6A 相关 lncRNA 与免疫浸润的相关性和预后价值。

方法

我们从 TCGA 数据库中下载了胃癌患者的临床相关信息和 RNA-Seq 转录组数据。采用单因素 Cox 回归分析和 Pearson 分析筛选出 m6A 相关 lncRNA。采用共识聚类分析将样本分为两个亚群,采用 LASSO 分析和 Cox 回归分析构建风险评分模型。

结果

共筛选出 25 个 lncRNA 表达谱,将胃癌患者分为不同亚型。Cluster 2 预后较好,但基质评分、ESTIMATE 评分和免疫评分较低。Cluster 1 富含静止记忆 CD4 T 细胞、调节性 T 细胞、单核细胞和静止肥大细胞,而 Cluster 2 富含活化记忆 CD4 T 细胞和滤泡辅助 T 细胞。选择 13 个 lncRNA 构建风险模型,高风险组胃癌患者预后较差。肿瘤中 PD-L1 的表达明显高于正常组织。单因素和多因素 Cox 回归分析结果表明,总生存率与分期和风险评分显著相关,可作为独立预后因素。热图和散点图的结果表明,聚类(P=0.0045)和分级(G1-2、G3,P=0.0037)与预后显著相关。风险评分与免疫细胞浸润的关系表明,记忆 B 细胞、静止树突状细胞、M0 巨噬细胞和 M2 巨噬细胞与风险评分呈正相关,而静止肥大细胞、单核细胞、活化自然杀伤细胞和滤泡辅助 T 细胞与风险评分呈负相关。

结论

本研究结果表明,m6A 相关 lncRNA 可能在胃癌患者的预后和肿瘤免疫微环境中发挥重要作用,可为胃癌患者的治疗提供帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6005/9310490/38e7919ea1ad/12920_2022_1318_Fig1_HTML.jpg

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