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鉴定乳腺癌患者中与乳腺癌脑转移相关的潜在基因。

Identification of potential genes related to breast cancer brain metastasis in breast cancer patients.

机构信息

Postdoctoral Research Station of Neurosurgery, Affiliated Hospital of Hebei University, Hebei University, Baoding, Hebei, China.

Department of Neurosurgery, Affiliated Hospital of Hebei University, Hebei University, Baoding, Hebei, China.

出版信息

Biosci Rep. 2021 Oct 29;41(10). doi: 10.1042/BSR20211615.

Abstract

Brain metastases (BMs) usually develop in breast cancer (BC) patients. Thus, the molecular mechanisms of breast cancer brain metastasis (BCBM) are of great importance in designing therapeutic strategies to treat or prevent BCBM. The present study attempted to identify novel diagnostic and prognostic biomarkers of BCBM. Two datasets (GSE125989 and GSE100534) were obtained from the Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs) in cases of BC with and without brain metastasis (BM). A total of 146 overlapping DEGs, including 103 up-regulated and 43 down-regulated genes, were identified. Functional enrichment analysis showed that these DEGs were mainly enriched for functions including extracellular matrix (ECM) organization and collagen catabolic fibril organization. Using protein-protein interaction (PPI) and principal component analysis (PCA) analysis, we identified ten key genes, including LAMA4, COL1A1, COL5A2, COL3A1, COL4A1, COL5A1, COL5A3, COL6A3, COL6A2, and COL6A1. Additionally, COL5A1, COL4A1, COL1A1, COL6A1, COL6A2, and COL6A3 were significantly associated with the overall survival of BC patients. Furthermore, COL6A3, COL5A1, and COL4A1 were potentially correlated with BCBM in human epidermal growth factor 2 (HER2) expression. Additionally, the miR-29 family might participate in the process of metastasis by modulating the cancer microenvironment. Based on datasets in the GEO database, several DEGs have been identified as playing potentially important roles in BCBM in BC patients.

摘要

脑转移(BMs)通常在乳腺癌(BC)患者中发展。因此,乳腺癌脑转移(BCBM)的分子机制在设计治疗策略以治疗或预防 BCBM 方面非常重要。本研究试图确定 BCBM 的新的诊断和预后生物标志物。从基因表达综合数据库(GEO)数据库中获得了两个数据集(GSE125989 和 GSE100534),以寻找有和无脑转移(BM)的乳腺癌病例中的差异表达基因(DEGs)。共鉴定出 146 个重叠的 DEGs,包括 103 个上调和 43 个下调基因。功能富集分析表明,这些 DEGs 主要富集在细胞外基质(ECM)组织和胶原蛋白代谢纤维组织的功能。通过蛋白质-蛋白质相互作用(PPI)和主成分分析(PCA)分析,我们确定了十个关键基因,包括 LAMA4、COL1A1、COL5A2、COL3A1、COL4A1、COL5A1、COL5A3、COL6A3、COL6A2 和 COL6A1。此外,COL5A1、COL4A1、COL1A1、COL6A1、COL6A2 和 COL6A3 与 BC 患者的总生存期显著相关。此外,COL6A3、COL5A1 和 COL4A1 可能与人类表皮生长因子 2(HER2)表达的 BCBM 相关。此外,miR-29 家族可能通过调节癌症微环境参与转移过程。基于 GEO 数据库中的数据集,已经确定了几个 DEG 在 BC 患者的 BCBM 中可能发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ad/8521534/b55eef950408/bsr-41-bsr20211615-g1.jpg

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