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一种用于结肠癌预后的新型炎症反应相关基因特征的鉴定与验证

Identification and Validation of a Novel Inflammatory Response-Related Gene Signature for the Prognosis of Colon Cancer.

作者信息

Liang Yichao, Wu Xin, Su Qi, Liu Yujie, Xiao Hong

机构信息

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.

出版信息

J Inflamm Res. 2021 Aug 11;14:3809-3821. doi: 10.2147/JIR.S321852. eCollection 2021.

Abstract

PURPOSE

The inflammatory response plays a crucial role in the occurrence and development of colon cancer. In this study, we aimed to explore a novel prognostic model for patients with colon cancer (COAD) based on inflammatory response-related genes.

METHODS

Inflammatory response-related genes were obtained from Molecular Signatures database. Univariate and multivariate Cox regression analyses were used for model construction based on TCGA dataset. GSE39582 dataset and qRT-PCR dataset were used for validation. Gene set variation analysis and gene set enrichment analysis were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT. Immunohistochemistry analysis and experiments were used to explore the function of genes in model.

RESULTS

In this study, a novel prognostic signature was identified using stepwise Cox proportional hazards regression analysis based on TCGA dataset. The results were subsequently validated in 562 patients from GSE39582 and a qRT-PCR data set from 70 tumor samples. Functional analysis indicated that the tumor microenvironment and immune cell infiltrate were different between high- and low-risk groups. Additionally, IHC results showed that the protein levels of prognostic genes were significantly different between COAD tissues and adjacent non-tumorous tissues, and prognostic genes could regulate the malignant phenotype of COAD cells.

CONCLUSION

Overall, the inflammation-related gene signature can be used for prognostic prediction in patients with COAD.

摘要

目的

炎症反应在结肠癌的发生和发展中起关键作用。在本研究中,我们旨在探索一种基于炎症反应相关基因的结肠癌(COAD)患者新型预后模型。

方法

从分子特征数据库中获取炎症反应相关基因。基于TCGA数据集,采用单变量和多变量Cox回归分析进行模型构建。使用GSE39582数据集和qRT-PCR数据集进行验证。进行基因集变异分析和基因集富集分析以探索潜在的调控途径。通过CIBERSORT分析免疫细胞浸润水平。采用免疫组织化学分析和实验来探索模型中基因的功能。

结果

在本研究中,基于TCGA数据集,使用逐步Cox比例风险回归分析确定了一种新型预后特征。随后在来自GSE39582的562例患者和来自70个肿瘤样本的qRT-PCR数据集中对结果进行了验证。功能分析表明,高风险组和低风险组之间的肿瘤微环境和免疫细胞浸润不同。此外,免疫组化结果显示,COAD组织与相邻非肿瘤组织之间预后基因的蛋白水平存在显著差异,且预后基因可调节COAD细胞的恶性表型。

结论

总体而言,炎症相关基因特征可用于COAD患者的预后预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81f/8364916/cead1471dd31/JIR-14-3809-g0001.jpg

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