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炎症对胃癌免疫微环境的影响

Effects of Inflammation on the Immune Microenvironment in Gastric Cancer.

作者信息

Zhao Weidan, Liu Mingqing, Zhang Mingyue, Wang Yachen, Zhang Yingli, Wang Shiji, Zhang Nan

机构信息

Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China.

Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, China.

出版信息

Front Oncol. 2021 Jul 23;11:690298. doi: 10.3389/fonc.2021.690298. eCollection 2021.

Abstract

BACKGROUND

Chronic inflammation and immune cell dysfunction in the tumor microenvironment are key factors in the development and progression of gastric tumors. However, inflammation-related genes associated with gastric cancer prognosis and their relationship with the expression of immune genes are not fully understood.

METHOD

In this study, we established an inflammatory response model score called "Riskscore", based on differentially expressed genes in gastric cancer. We used Survival and Survminer packages in R to analyze patient survival and prognosis in risk groups. The survival curve was plotted using the Kaplan-Meier method, and the log-rank test was used to assess statistical significance, and we performed the ROC analysis using the R language package to analyze the 1-, 3-, and 5-year survival of patients in the GEO and TCGA databases. Single-factor and multi-factor prognostic analyses were carried out for age, sex, T, N, M, and risk score. Pathway enrichment analysis indicated immune factor-related pathway enrichment in both patient groups. Next, we screened for important genes that are involved in immune cell regulation. Finally, we created a correlation curve to explore the correlation between Riskscore and the expression of these genes.

RESULTS

The prognosis was significantly different between high- and low-risk groups, and the survival rate and survival time of the high-risk group were lower than those of the low-risk group. we found that the pathways related to apoptosis, hypoxia, and immunity were most enriched in the risk groups. we found two common tumor-infiltrating immune cell types (i.e., follicular helper T cells and resting dendritic cells) between the two risk groups and identified 10 genes that regulate these cells. Additionally, we found that these 10 genes are positively associated with the two risk groups.

CONCLUSION

Finally, a risk model of the inflammatory response in gastric cancer was established, and the inflammation-related genes used to construct the model were found to be directly related to immune infiltration. This model can improve the gastric cancer prognosis prediction. Our findings contribute to the development of immunotherapy for the treatment of gastric cancer patients.

摘要

背景

肿瘤微环境中的慢性炎症和免疫细胞功能障碍是胃肿瘤发生和发展的关键因素。然而,与胃癌预后相关的炎症相关基因及其与免疫基因表达的关系尚未完全明确。

方法

在本研究中,我们基于胃癌中差异表达基因建立了一种名为“风险评分(Riskscore)”的炎症反应模型评分。我们使用R语言中的Survival和Survminer软件包分析风险组患者的生存情况和预后。采用Kaplan-Meier法绘制生存曲线,并用对数秩检验评估统计学意义,同时使用R语言软件包进行ROC分析,以分析GEO和TCGA数据库中患者的1年、3年和5年生存率。对年龄、性别、T、N、M和风险评分进行单因素和多因素预后分析。通路富集分析表明,两组患者中均存在免疫因子相关通路富集。接下来,我们筛选了参与免疫细胞调节的重要基因。最后,我们绘制了相关曲线,以探讨Riskscore与这些基因表达之间的相关性。

结果

高风险组和低风险组的预后存在显著差异,高风险组的生存率和生存时间低于低风险组。我们发现与凋亡、缺氧和免疫相关的通路在风险组中富集程度最高。我们在两个风险组中发现了两种常见的肿瘤浸润免疫细胞类型(即滤泡辅助性T细胞和静息树突状细胞),并鉴定出10个调节这些细胞的基因。此外,我们发现这10个基因与两个风险组呈正相关。

结论

最终,我们建立了胃癌炎症反应风险模型,发现用于构建该模型的炎症相关基因与免疫浸润直接相关。该模型可以改善胃癌预后预测。我们的研究结果有助于开发针对胃癌患者的免疫治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc93/8343517/33412cd29b31/fonc-11-690298-g001.jpg

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