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Comprehensive analysis of EMT-related genes and lncRNAs in the prognosis, immunity, and drug treatment of colorectal cancer
Journal of Translational Medicine ( IF 7.4 ) Pub Date : 2021-09-15 , DOI: 10.1186/s12967-021-03065-0
Yang Yang 1, 2 , Mingyang Feng 1, 2 , LiangLiang Bai 1, 2 , Weiting Liao 1, 2 , Kexun Zhou 1, 2 , Mengxi Zhang 1, 2 , Qiuji Wu 1, 2 , Feng Wen 1, 2 , Wanting Lei 1, 2 , Pengfei Zhang 1, 2 , Nan Zhang 1, 2 , Jiaxing Huang 1, 2 , Qiu Li 1, 2
Affiliation  

EMT is an important biological process in the mechanism of tumor invasion and metastasis. However, there are still many unknowns about the specific mechanism of EMT in tumor. At present, a comprehensive analysis of EMT-related genes in colorectal cancer (CRC) is still lacking. All the data were downloaded from public databases including TCGA database (488 tumor samples and 52 normal samples) as the training set and the GEO database (GSE40967 including 566 tumor samples and 19 normal samples, GSE12945 including 62 tumor samples, GSE17536 including 177 tumor samples, GSE17537 including 55 tumor samples) as the validation sets. One hundred and sixty-six EMT-related genes (EMT-RDGs) were selected from the Molecular Signatures Database. Bioinformatics methods were used to analyze the correlation between EMT-RDGs and CRC prognosis, metastasis, drug efficacy, and immunity. We finally obtained nine prognostic-related EMT-RDGs (FGF8, NOG, PHLDB2, SIX2, SNAI1, TBX5, TIAM1, TWIST1, TCF15) through differential expression analysis, Unicox and Lasso regression analysis, and then constructed a risk prognosis model. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high-risk and low-risk groups and the different states of the nine prognostic-related EMT-RDGs. The methylation level and mutation status of nine prognostic-related EMT-RDGs all affect their regulation of EMT. The Cox proportional hazards regression model was also constructed by the methylation sites of nine prognostic-related EMT-RDGs. In addition, the expression of FGF8, PHLDB2, SIX2, and SNAIL was higher and the expression level of NOG and TWIST1 was lower in the non-metastasis CRC group. Nine prognostic-related EMT-RDGs also affected the drug treatment response of CRC. Targeting these nine prognostic-related EMT-RDGs can regulate CRC metastasis and immune, which is beneficial for the prognosis of CRC patients, improve drug sensitivity in CRC patients.

中文翻译:

EMT相关基因和lncRNA在结直肠癌预后、免疫和药物治疗中的综合分析

EMT是肿瘤侵袭转移机制中的一个重要生物学过程。然而,关于EMT在肿瘤中的具体机制仍有许多未知。目前,还缺乏对结直肠癌(CRC)中EMT相关基因的综合分析。所有数据均从公共数据库下载,包括TCGA数据库(488个肿瘤样本和52个正常样本)作为训练集和GEO数据库(GSE40967包括566个肿瘤样本和19个正常样本,GSE12945包括62个肿瘤样本,GSE17536包括177个肿瘤样本) , GSE17537 包括 55 个肿瘤样本)作为验证集。从分子特征数据库中选择了 166 个 EMT 相关基因 (EMT-RDG)。采用生物信息学方法分析EMT-RDGs与CRC预后、转移、转移的相关性。药效、免疫力。我们最终通过差异表达分析、Un​​icox 和 Lasso 回归分析获得了 9 个与预后相关的 EMT-RDGs(FGF8、NOG、PHLDB2、SIX2、SNAI1、TBX5、TIAM1、TWIST1、TCF15),并构建了风险预后模型。高危组和低危组之间以及9种预后相关EMT-RDGs的不同状态在临床特征、22种免疫细胞和免疫功能方面存在显着差异。九个与预后相关的 EMT-RDG 的甲基化水平和突变状态都会影响它们对 EMT 的调节。Cox 比例风险回归模型也由九个与预后相关的 EMT-RDG 的甲基化位点构建。此外,FGF8、PHLDB2、SIX2、非转移CRC组SNAIL较高,NOG和TWIST1表达水平较低。九个与预后相关的 EMT-RDG 也影响了 CRC 的药物治疗反应。针对这 9 种与预后相关的 EMT-RDGs 可以调节 CRC 转移和免疫,有利于 CRC 患者的预后,提高 CRC 患者的药物敏感性。
更新日期:2021-09-16
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