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雄激素受体阳性三阴性乳腺癌的枢纽基因和治疗药物的筛选的综合生物信息学分析。

Integrated Bioinformatics Analysis for the Screening of Hub Genes and Therapeutic Drugs in Androgen Receptor-Positive TNBC.

机构信息

Thyroid & Breast Surgery, The Second Affiliated Hospital of Fujian Medical University, 950 Donghai Street, Quanzhou, China.

出版信息

Dis Markers. 2022 Sep 14;2022:4964793. doi: 10.1155/2022/4964793. eCollection 2022.

Abstract

As the most invasive and lethal subtype of breast cancer (BC), triple-negative breast carcinoma (TNBC) is of increasing interest. However, the androgen receptor (AR) still has an unclear role in TNBC. The current study is aimed at testing the diagnostic and therapeutic performance of novel biomarkers for AR-positive TNBC. The GSE76124 dataset was analyzed by combining WGCNA and other bioinformatics methods. Subsequently, function enrichment analysis was applied to identify the relationships between these differential expression genes (DEGs). Subsequently, the protein-protein interaction network was established, and the hub genes were identified by Cytoscape software. Eventually, the miRNA-hub gene modulate network was developed and the Drug-Gene Interaction Database (DGIdb) was applied to verify the potential drugs for AR-positive TNBC. In the current research, 88 DEGs in total were selected from the intersection of the purple module genes identified by WGCNA and limma package. TFF1, FOXA1, ESR1, AGR2, TFF3, AGR3, GATA3, XBP1, SPDEF, and TOX3 were selected as hub genes by the MCC method, which were all upregulated. The survival analysis suggested that TFF1 was the only one related to significant lower survival rate in TNBC. Ultimately, hsa-miR-520g-3p and hsa-miR-520h were found taking part in the regulation of TFF1, and 2 small molecules were identified as the potential targets for AR-positive TNBC treatment. As a result, our study suggested that hsa-miR-520g-3p, hsa-miR-520h, and TFF1 might have significant potential values for AR-positive TNBC diagnosis and prognosis prediction. TFF1, hsa-miR-520g-3, and hsa-miR-520h may serve as the novel therapeutic targets, and our findings offer further insights into the therapy of AR-positive TNBC.

摘要

作为最具侵袭性和致命性的乳腺癌(BC)亚型,三阴性乳腺癌(TNBC)越来越受到关注。然而,雄激素受体(AR)在 TNBC 中的作用仍不清楚。本研究旨在测试 AR 阳性 TNBC 的新型生物标志物的诊断和治疗性能。通过结合 WGCNA 和其他生物信息学方法分析 GSE76124 数据集。随后,应用功能富集分析来识别这些差异表达基因(DEG)之间的关系。随后,建立蛋白质-蛋白质相互作用网络,并通过 Cytoscape 软件识别枢纽基因。最终,开发了 miRNA-枢纽基因调节网络,并应用 Drug-Gene Interaction Database(DGIdb)验证 AR 阳性 TNBC 的潜在药物。在本研究中,总共从 WGCNA 和 limma 包鉴定的紫色模块基因的交集选择了 88 个 DEG。通过 MCC 方法选择 TFF1、FOXA1、ESR1、AGR2、TFF3、AGR3、GATA3、XBP1、SPDEF 和 TOX3 作为枢纽基因,这些基因均上调。生存分析表明,TFF1 是唯一与 TNBC 生存率显著降低相关的基因。最终,发现 hsa-miR-520g-3p 和 hsa-miR-520h 参与了 TFF1 的调节,并且鉴定出 2 种小分子作为 AR 阳性 TNBC 治疗的潜在靶点。因此,我们的研究表明,hsa-miR-520g-3p、hsa-miR-520h 和 TFF1 可能对 AR 阳性 TNBC 的诊断和预后预测具有显著的潜在价值。TFF1、hsa-miR-520g-3 和 hsa-miR-520h 可能作为新的治疗靶点,我们的研究结果为 AR 阳性 TNBC 的治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb03/9493148/f7a9ebf4db9b/DM2022-4964793.001.jpg

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