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利用公开可用的转录组数据进行计算机分析以鉴定三阴性乳腺癌特异性生物标志物

In Silico Analysis of Publicly Available Transcriptomic Data for the Identification of Triple-Negative Breast Cancer-Specific Biomarkers.

作者信息

Kaddoura Rachid, Alqutami Fatma, Asbaita Mohamed, Hachim Mahmood

机构信息

College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates.

出版信息

Life (Basel). 2023 Feb 2;13(2):422. doi: 10.3390/life13020422.

Abstract

BACKGROUND

Breast cancer is the most common type of cancer among women and is classified into multiple subtypes. Triple-negative breast cancer (TNBC) is the most aggressive subtype, with high mortality rates and limited treatment options such as chemotherapy and radiation. Due to the heterogeneity and complexity of TNBC, there is a lack of reliable biomarkers that can be used to aid in the early diagnosis and prognosis of TNBC in a non-invasive screening method.

AIM

This study aims to use in silico methods to identify potential biomarkers for TNBC screening and diagnosis, as well as potential therapeutic markers.

METHODS

Publicly available transcriptomic data of breast cancer patients published in the NCBI's GEO database were used in this analysis. Data were analyzed with the online tool GEO2R to identify differentially expressed genes (DEGs). Genes that were differentially expressed in more than 50% of the datasets were selected for further analysis. Metascape, Kaplan-Meier plotter, cBioPortal, and the online tool TIMER were used for functional pathway analysis to identify the biological role and functional pathways associated with these genes. Breast Cancer Gene-Expression Miner v4.7 was used to validify the obtained results in a larger cohort of datasets.

RESULTS

A total of 34 genes were identified as differentially expressed in more than half of the datasets. The DEG GATA3 had the highest degree of regulation, and it plays a role in regulating other genes. The estrogen-dependent pathway was the most enriched pathway, involving four crucial genes, including GATA3. The gene FOXA1 was consistently down-regulated in TNBC in all datasets.

CONCLUSIONS

The shortlisted 34 DEGs will aid clinicians in diagnosing TNBC more accurately as well as developing targeted therapies to improve patient prognosis. In vitro and in vivo studies are further recommended to validate the results of the current study.

摘要

背景

乳腺癌是女性中最常见的癌症类型,可分为多种亚型。三阴性乳腺癌(TNBC)是最具侵袭性的亚型,死亡率高,治疗选择有限,如化疗和放疗。由于TNBC的异质性和复杂性,缺乏可靠的生物标志物可用于非侵入性筛查方法辅助TNBC的早期诊断和预后评估。

目的

本研究旨在使用计算机方法识别用于TNBC筛查和诊断的潜在生物标志物以及潜在的治疗标志物。

方法

本分析使用了NCBI的GEO数据库中公开的乳腺癌患者转录组数据。使用在线工具GEO2R分析数据以识别差异表达基因(DEG)。选择在超过50%的数据集中差异表达的基因进行进一步分析。使用Metascape、Kaplan-Meier plotter、cBioPortal和在线工具TIMER进行功能通路分析,以识别与这些基因相关的生物学作用和功能通路。使用乳腺癌基因表达挖掘器v4.7在更大的数据集队列中验证所得结果。

结果

共鉴定出34个基因在超过一半的数据集中差异表达。DEG GATA3的调控程度最高,它在调节其他基因中发挥作用。雌激素依赖性通路是最富集的通路,涉及四个关键基因,包括GATA3。在所有数据集中,基因FOXA1在TNBC中始终下调。

结论

入围的34个DEG将有助于临床医生更准确地诊断TNBC,并开发靶向治疗以改善患者预后。进一步建议进行体外和体内研究以验证本研究结果。

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