通过加权基因共表达网络分析鉴定与三阴性乳腺癌无病生存相关的转录因子。

IF 3.1 4区 医学 Q2 PATHOLOGY
Cytojournal Pub Date : 2024-12-23 eCollection Date: 2024-01-01 DOI:10.25259/Cytojournal_127_2024
Huipo Wang, Ran Hao, Wei Liu, Yi Zhang, Shen Ma, Yiwei Lu, Jie Hu, Yixin Qi
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引用次数: 0

摘要

目的:三阴性乳腺癌(triple negative breast cancer, TNBC)是一种复发转移率高、预后较其他乳腺癌亚型差的乳腺癌亚型。本研究的目的是确定与TNBC无病生存期(DFS)相关的调节因子和TNBC治疗的潜在生物标志物。材料和方法:我们从Gene Expression Omnibus网站获取GSE97342数据集,进行加权基因共表达网络分析(weighted Gene co-expression network analysis, WGCNA),识别与TNBC DFS相关的模块。随后,通过基因本体(GO)和京都基因与基因组百科全书(KEGG)途径分析阐明了模块的生物学功能。通过对重叠转录因子的单变量Cox回归分析,与Human Transcription Factor Database交叉核对有助于选择枢纽转录因子。利用生物信息学分析,我们评估了这些枢纽转录因子的预后意义,研究了它们的靶基因,并探讨了它们与TNBC中肿瘤免疫细胞的关系。最后,通过免疫组织化学染色、定量逆转录聚合酶链反应(qRT-PCR)和Western blotting验证枢纽转录因子的表达水平。结果:通过WGCNA分析,我们确定了与TNBC患者DFS相关的三个模块。GO和KEGG分析阐明了这些模块中基因的生物学功能。生存分析确定了三个枢纽转录因子:叉头盒D1 (FOXD1)、芳烃受体核转运因子2 (ARNT2)和锌指蛋白132 (ZNF132)。FOXD1的表达水平与TNBC患者的预后呈负相关,而其他两个基因与TNBC患者的预后呈正相关。免疫组化染色、qRT-PCR和Western blotting验证了枢纽转录因子的表达水平。结论:我们发现三个枢纽转录因子(FOXD1、ARNT2和ZNF132)与TNBC的DFS相关。这些相关性表明它们有可能作为三阴癌患者的预后预测因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identification of transcription factors associated with the disease-free survival of triple-negative breast cancer through weighted gene co-expression network analysis.

Identification of transcription factors associated with the disease-free survival of triple-negative breast cancer through weighted gene co-expression network analysis.

Identification of transcription factors associated with the disease-free survival of triple-negative breast cancer through weighted gene co-expression network analysis.

Identification of transcription factors associated with the disease-free survival of triple-negative breast cancer through weighted gene co-expression network analysis.

Objective: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that has a worse prognosis than the other subtypes of breast cancer because of its high recurrence and metastasis rates. The objective of this study is to identify the regulatory factors that are associated with the disease-free survival (DFS) of TNBC and potential biomarkers for TNBC treatment.

Material and methods: We obtained the GSE97342 dataset from the Gene Expression Omnibus website and conducted weighted gene co-expression network analysis (WGCNA) to identify modules associated with the DFS of TNBC. Subsequently, biological functions of the modules were elucidated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Cross-checking with the Human Transcription Factor Database facilitated the selection of hub transcription factors through univariate Cox regression analysis of overlapping transcription factors. Utilizing bioinformatics analysis, we assessed the prognostic significance of these hub transcription factors, investigated their target genes, and explored their associations with tumor immune cells in TNBC. Finally, the expression levels of the hub transcription factors were validated by immunohistochemical staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting.

Results: Through WGCNA analysis, we identified three modules correlated with DFS in TNBC. GO and KEGG analyses elucidated the biological functions of genes within these modules. Survival analysis pinpointed three hub transcription factors: Forkhead box D1 (FOXD1), aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), and zinc finger protein 132 (ZNF132). The expression level of FOXD1 was negatively associated with the prognoses of patients with TNBC, whereas the other two genes were positively associated with the prognoses of patients with TNBC. Immunohistochemical staining, qRT-PCR, and Western blotting validated the expression levels of the hub transcription factors.

Conclusion: We discovered three hub transcription factors (FOXD1, ARNT2, and ZNF132) that were correlated with the DFS of TNBC. These correlations suggested their potential as prognostic predictors for patients with TNBC.

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来源期刊
Cytojournal
Cytojournal PATHOLOGY-
CiteScore
2.20
自引率
42.10%
发文量
56
审稿时长
>12 weeks
期刊介绍: The CytoJournal is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Diagnostic Cytopathology including Molecular aspects. The journal is owned by the Cytopathology Foundation and published by the Scientific Scholar.
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