胃腺癌幽门螺杆菌感染的预后风险评分模型。

Jing Peng, Qi Yan, Wennan Pei, Yi Jiang, Li Zhou, Ruoqing Li
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引用次数: 0

摘要

背景:幽门螺杆菌(Helicobacter pylori, HP)与多种胃疾病的发生有关,是胃腺癌(STAD)的主要危险因素之一。方法:采用单样本基因集富集分析(ssGSEA)方法比较肿瘤组与正常组HP感染评分。通过加权基因共表达网络分析(WGCNA)鉴定出与HP感染相关的关键模块,并对这些模块基因进行功能富集分析。进一步,利用limma包筛选hp阳性和hp阴性STAD之间的差异表达基因(DEGs)。获取预后基因构建风险评分模型,并对模型的性能进行验证。采用Spearman法分析风险评分与肿瘤免疫微环境(TIME)的相关性。绘制hp阳性STAD单细胞图谱。通过STAD细胞验证预后基因mRNA表达水平,并通过伤口愈合实验和transwell实验评估STAD细胞的迁移和侵袭能力。结果:肿瘤组HP感染评分明显高于正常组。紫色和宝蓝色模块与STAD中HP感染的相关性较高,并且这些模块基因在免疫相关途径中富集。进一步,从HP感染相关deg中筛选出5个预后基因(CTLA4、CPVL、EMB、CXCR4和FAM241A),用于建立风险评分模型,稳健性较好。STAD患者的风险评分与时间有较强的相关性。hp阳性STAD的单细胞图谱显示,CXCR4在肿瘤组上皮细胞1、上皮细胞2和壁细胞中高表达。CPVL、EMB、CTLA4、FAM241A、CXCR4在STAD细胞中高表达,沉默CPVL可抑制STAD细胞的迁移和侵袭。结论:本研究建立了基于HP感染相关基因的风险评分模型,可为STAD的预后预测及治疗靶点提供参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A Prognostic Riskscore Model Related to Helicobacter pylori Infection in Stomach Adenocarcinoma

A Prognostic Riskscore Model Related to Helicobacter pylori Infection in Stomach Adenocarcinoma

Background: Helicobacter pylori (HP) is associated with the development of various stomach diseases, one of the major risk factors for stomach adenocarcinoma (STAD).

Methods: The HP infection score between tumor and normal groups was compared by single-sample gene set enrichment analysis (ssGSEA). The key modules related to HP infection were identified by weighted gene coexpression network analysis (WGCNA), and functional enrichment analysis was conducted on these module genes. Further, the limma package was used to screen the differentially expressed genes (DEGs) between HP-positive and HP-negative STAD. The prognostic genes were obtained to construct the riskscore model, and the performance of the model was validated. The correlation between riskscore and tumor immune microenvironment (TIME) was analyzed by Spearman’s method. The single-cell atlas of HP-positive STAD was delineated. The mRNA expression levels of the prognostic genes were verified using STAD cells, and the migration and invasion capacities of STAD cells were evaluated by using the wound healing assay and transwell assay.

Results: The HP infection score in the tumor group was significantly higher than that in the normal group. The purple and royal blue modules showed higher correlation with HP infection in STAD, and these module genes were enriched in the immune-related pathway. Further, five prognostic genes (CTLA4, CPVL, EMB, CXCR4, and FAM241A) were screened from the HP infection–related DEGs, which were utilized for establishing the riskscore model, with good robustness. Riskscore exhibited strong correlation with TIME in STAD. Single-cell atlas of HP-positive STAD revealed that CXCR4 is highly expressed in Epithelial Cell 1, Epithelial Cell 2, and parietal cells of the tumor group. CPVL, EMB, CTLA4, FAM241A, and CXCR4 showed high expression in STAD cells, and the silencing of CPVL could suppress the migration and invasion of STAD cells.

Conclusion: This study established a riskscore model based on HP infection–related genes, which could provide reference for prognostic prediction and treatment targets of STAD.

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Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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