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基于加权基因共表达网络分析(WGCNA)鉴定局部晚期乳腺癌患者治疗反应中的潜在靶点和通路。

WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients.

作者信息

Zhao Ruipeng, Wei Wan, Zhen Linlin

机构信息

Department of Thyroid and Breast Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.

出版信息

Open Med (Wars). 2023 Mar 6;18(1):20230651. doi: 10.1515/med-2023-0651. eCollection 2023.

Abstract

Locally advanced breast cancer patients have a poor prognosis; however, the relationship between potential targets and the response to treatment is still unclear. The gene expression profiles of breast cancer patients with stages from IIB to IIIC were downloaded from The Cancer Genome Atlas. We applied weighted gene co-expression network analysis and differentially expressed gene analysis to identify the primary genes involved in treatment response. The disease-free survival between low- and high-expression groups was analyzed using Kaplan-Meier analysis. Gene set enrichment analysis was applied to identify hub genes-related pathways. Additionally, the CIBERSORT algorithm was employed to evaluate the correlation between the hub gene expression and immune cell types. A total of 16 genes were identified to be related to radiotherapy response, and low expression of SVOPL, EDAR, GSTA1, and ABCA13 was associated with poor overall survival and progression-free survival in breast cancer cases. Correlation analysis revealed that the four genes negatively related to some specific immune cell types. The four genes were downregulated in H group compared with the L group. Four hub genes associated with the immune cell infiltration of breast cancer were identified; these genes might be used as a promising biomarker to test the treatment in breast cancer patients.

摘要

局部晚期乳腺癌患者预后较差;然而,潜在靶点与治疗反应之间的关系仍不清楚。从癌症基因组图谱下载了IIB期至IIIC期乳腺癌患者的基因表达谱。我们应用加权基因共表达网络分析和差异表达基因分析来确定参与治疗反应的主要基因。使用Kaplan-Meier分析对低表达组和高表达组之间的无病生存期进行分析。应用基因集富集分析来确定与枢纽基因相关的通路。此外,采用CIBERSORT算法评估枢纽基因表达与免疫细胞类型之间的相关性。共鉴定出16个与放疗反应相关的基因,SVOPL、EDAR、GSTA1和ABCA13的低表达与乳腺癌患者的总生存期和无进展生存期较差有关。相关性分析显示,这四个基因与某些特定免疫细胞类型呈负相关。与L组相比,H组中这四个基因表达下调。鉴定出四个与乳腺癌免疫细胞浸润相关的枢纽基因;这些基因可能作为一种有前景的生物标志物,用于检测乳腺癌患者的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4450/9990777/abc44789ae78/j_med-2023-0651-fig001.jpg

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