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通过机器学习方法鉴定食管鳞状细胞癌中与m6a相关的特征基因

Identification of m6a-related signature genes in esophageal squamous cell carcinoma by machine learning method.

作者信息

Shang Qi-Xin, Kong Wei-Li, Huang Wen-Hua, Xiao Xin, Hu Wei-Peng, Yang Yu-Shang, Zhang Hanlu, Yang Lin, Yuan Yong, Chen Long-Qi

机构信息

West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Front Genet. 2023 Jan 17;14:1079795. doi: 10.3389/fgene.2023.1079795. eCollection 2023.

Abstract

We aimed to construct and validate the esophageal squamous cell carcinoma (ESCC)-related m6A regulators by means of machine leaning. We used ESCC RNA-seq data of 66 pairs of ESCC from West China Hospital of Sichuan University and the transcriptome data extracted from The Cancer Genome Atlas (TCGA)-ESCA database to find out the ESCC-related m6A regulators, during which, two machine learning approaches: RF (Random Forest) and SVM (Support Vector Machine) were employed to construct the model of ESCC-related m6A regulators. Calibration curves, clinical decision curves, and clinical impact curves (CIC) were used to evaluate the predictive ability and best-effort ability of the model. Finally, western blot and immunohistochemistry staining were used to assess the expression of prognostic ESCC-related m6A regulators. 2 m6A regulators (YTHDF1 and HNRNPC) were found to be significantly increased in ESCC tissues after screening out through RF machine learning methods from our RNA-seq data and TCGA-ESCA database, respectively, and overlapping the results of the two clusters. A prognostic signature, consisting of YTHDF1 and HNRNPC, was constructed based on our RNA-seq data and validated on TCGA-ESCA database, which can serve as an independent prognostic predictor. Experimental validation including the western and immunohistochemistry staining were further successfully confirmed the results of bioinformatics analysis. We constructed prognostic ESCC-related m6A regulators and validated the model in clinical ESCC cohort as well as in ESCC tissues, which provides reasonable evidence and valuable resources for prognostic stratification and the study of potential targets for ESCC.

摘要

我们旨在通过机器学习构建并验证与食管鳞状细胞癌(ESCC)相关的m6A调控因子。我们使用了四川大学华西医院66对ESCC的RNA测序数据以及从癌症基因组图谱(TCGA)-ESCA数据库中提取的转录组数据来找出与ESCC相关的m6A调控因子,在此过程中,采用了两种机器学习方法:随机森林(RF)和支持向量机(SVM)来构建与ESCC相关的m6A调控因子模型。校准曲线、临床决策曲线和临床影响曲线(CIC)用于评估该模型的预测能力和最佳努力能力。最后,使用蛋白质免疫印迹和免疫组织化学染色来评估与ESCC预后相关的m6A调控因子的表达。通过分别从我们的RNA测序数据和TCGA-ESCA数据库中采用RF机器学习方法筛选后,发现2个m6A调控因子(YTHDF1和HNRNPC)在ESCC组织中显著增加,并且两个聚类结果相互重叠。基于我们的RNA测序数据构建了一个由YTHDF1和HNRNPC组成的预后特征,并在TCGA-ESCA数据库上进行了验证,该特征可作为一个独立的预后预测指标。包括蛋白质免疫印迹和免疫组织化学染色在内的实验验证进一步成功证实了生物信息学分析的结果。我们构建了与ESCC预后相关的m6A调控因子,并在临床ESCC队列以及ESCC组织中验证了该模型,这为ESCC的预后分层和潜在靶点研究提供了合理的证据和宝贵的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43f/9886874/02ee9aeb5ce6/fgene-14-1079795-g001.jpg

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