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基于 TCGA 和 GEO 数据的综合分析鉴定与食管癌放射敏感性相关的 miRNA-mRNA 调控网络。

Identification of the miRNA-mRNA regulatory network associated with radiosensitivity in esophageal cancer based on integrative analysis of the TCGA and GEO data.

机构信息

Cancer Center, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu, 610041, People's Republic of China.

Department of Medical Oncology, Chengdu Shang Jin Nan Fu Hospital (West China Hospital, S.C.U.), Chengdu, 611730, People's Republic of China.

出版信息

BMC Med Genomics. 2022 Dec 1;15(1):249. doi: 10.1186/s12920-022-01392-9.

Abstract

BACKGROUND

The current study set out to identify the miRNA-mRNA regulatory networks that influence the radiosensitivity in esophageal cancer based on the The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases.

METHODS

Firstly, esophageal cancer-related miRNA-seq and mRNA-seq data were retrieved from the TCGA database, and the mRNA dataset of esophageal cancer radiotherapy was downloaded from the GEO database to analyze the differential expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in radiosensitive and radioresistant samples, followed by the construction of the miRNA-mRNA regulatory network and Gene Ontology and KEGG enrichment analysis. Additionally, a prognostic risk model was constructed, and its accuracy was evaluated by means of receiver operating characteristic analysis.

RESULTS

A total of 125 DEmiRNAs and 42 DEmRNAs were closely related to the radiosensitivity in patients with esophageal cancer. Based on 47 miRNA-mRNA interactions, including 21 miRNAs and 21 mRNAs, the miRNA-mRNA regulatory network was constructed. The prognostic risk model based on 2 miRNAs (miR-132-3p and miR-576-5p) and 4 mRNAs (CAND1, ZDHHC23, AHR, and MTMR4) could accurately predict the prognosis of esophageal cancer patients. Finally, it was verified that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR could affect the radiosensitivity in esophageal cancer.

CONCLUSION

Our study demonstrated that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR were critical molecular pathways related to the radiosensitivity of esophageal cancer.

摘要

背景

本研究旨在基于癌症基因组图谱(TCGA)和基因表达综合数据库(GEO),确定影响食管癌放射敏感性的 miRNA-mRNA 调控网络。

方法

首先从 TCGA 数据库中检索与食管癌相关的 miRNA-seq 和 mRNA-seq 数据,并从 GEO 数据库中下载食管癌放疗的 mRNA 数据集,以分析放射敏感和放射抵抗样本中的差异表达 miRNA(DEmiRNAs)和 mRNAs(DEmRNAs),然后构建 miRNA-mRNA 调控网络,并进行基因本体论和京都基因与基因组百科全书通路富集分析。此外,构建了一个预后风险模型,并通过接受者操作特征分析评估其准确性。

结果

共鉴定出 125 个与食管癌患者放射敏感性密切相关的 DEmiRNAs 和 42 个 DEmRNAs。基于 47 个 miRNA-mRNA 相互作用,包括 21 个 miRNA 和 21 个 mRNAs,构建了 miRNA-mRNA 调控网络。基于 2 个 miRNA(miR-132-3p 和 miR-576-5p)和 4 个 mRNAs(CAND1、ZDHHC23、AHR 和 MTMR4)的预后风险模型能够准确预测食管癌患者的预后。最后,验证了 miR-132-3p/CAND1/ZDHHC23 和 miR-576-5p/AHR 可以影响食管癌的放射敏感性。

结论

本研究表明,miR-132-3p/CAND1/ZDHHC23 和 miR-576-5p/AHR 是与食管癌放射敏感性相关的关键分子途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c422/9714096/dd4d8e8ea0f3/12920_2022_1392_Fig1_HTML.jpg

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