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三阴性乳腺癌预后不良潜在生物标志物的综合生物信息学分析

Integrated bioinformatic analysis of potential biomarkers of poor prognosis in triple-negative breast cancer.

作者信息

Bissanum Rassanee, Kamolphiwong Rawikant, Navakanitworakul Raphatphorn, Kanokwiroon Kanyanatt

机构信息

Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

出版信息

Transl Cancer Res. 2022 Sep;11(9):3039-3049. doi: 10.21037/tcr-22-662.

Abstract

BACKGROUND

Triple-negative breast cancer (TNBC) is a heterogeneous disease associated with late-stage diagnosis and high metastatic rates. However, a gene signature for reliable TNBC biomarkers is not available yet. We aimed to identify potential key genes and their association with poor prognosis in TNBC through integrated bioinformatics.

METHODS

Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in TNBC non-TNBC and TNBC . normal tissues were analyzed. Overlapping upregulated and downregulated DEGs were selected as inputs for Gene Ontology and pathway enrichment analyses using Metascape. Then, UALCAN and Kaplan-Meier plotter were employed to analyze the prognostic values of all overlapping DEGs.

RESULTS

We identified 21 upregulated and 24 downregulated overlapping DEGs in TNBC non-TNBC and TNBC normal breast tissue. The upregulated overlapping DEGs were mainly enriched in various pathways including chromosome segregation, cell cycle phase transition, and cell division, whereas overlapping DEGs were significantly downregulated in pathways, such as multicellular organismal homeostasis, tissue homeostasis, and negative regulation of cell population proliferation. Key genes were identified by association with poor overall survival (OS). Our results showed that high expression of and was associated with poor OS of TNBC patients. Conversely, the low expression of , and indicated worse OS.

CONCLUSIONS

We identified key genes (, and ) associated with poor OS. Thus, these genes might serve as candidate prognostic markers for TNBC.

摘要

背景

三阴性乳腺癌(TNBC)是一种异质性疾病,与晚期诊断和高转移率相关。然而,目前尚无用于可靠的TNBC生物标志物的基因特征。我们旨在通过整合生物信息学来鉴定TNBC中潜在的关键基因及其与不良预后的关联。

方法

从基因表达综合数据库(GEO)下载微阵列数据集。分析TNBC与非TNBC以及TNBC与正常组织中的差异表达基因(DEG)。选择重叠的上调和下调DEG作为使用Metascape进行基因本体论和通路富集分析的输入。然后,使用UALCAN和Kaplan-Meier绘图仪分析所有重叠DEG的预后价值。

结果

我们在TNBC与非TNBC以及TNBC与正常乳腺组织中鉴定出21个上调和24个下调的重叠DEG。上调的重叠DEG主要富集于各种通路,包括染色体分离、细胞周期阶段转变和细胞分裂,而重叠DEG在多细胞生物体稳态、组织稳态和细胞群体增殖的负调控等通路中显著下调。通过与不良总生存期(OS)的关联鉴定出关键基因。我们的结果表明,[具体基因1]和[具体基因2]的高表达与TNBC患者的不良OS相关。相反,[具体基因3]、[具体基因4]和[具体基因5]的低表达表明OS较差。

结论

我们鉴定出与不良OS相关的关键基因([具体基因1]、[具体基因3]、[具体基因4]和[具体基因5])。因此,这些基因可能作为TNBC的候选预后标志物。

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