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采用网络互作分析方法鉴定分泌组中潜在的乳腺癌干细胞生物标志物。

Identification of Potential Breast Cancer Stem Cell Biomarkers in the Secretome Using a Network Interaction Approach Analysis.

机构信息

Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta, 10430, Indonesia.

Molecular Biology and Proteomics Core Facilities, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta, 10430, Indonesia.

出版信息

Asian Pac J Cancer Prev. 2024 May 1;25(5):1803-1813. doi: 10.31557/APJCP.2024.25.5.1803.

Abstract

BACKGROUND

Breast cancer stem cells (BCSCs) play a role in the high rates of resistance, recurrence, and metastasis. The precise biomarkers of BCSCs can assist effectively in identifying cancer, assessing prognosis, diagnosing, and monitoring therapy. The aim of this study was to give a complete analysis for predicting specific biomarkers of BCSCs.

METHODS

We aggregated profile datasets in this work to shed light on the underlying critical genes and pathways of BCSCs. We obtained two expression profiling by array datasets (GSE7513 and GSE7515) from the Gene Expression Omnibus (GEO) database to identify biomarkers in BCSCs. Enrichr was used to do functional analysis, including gene ontology (GO) and reactome pathway. Furthermore, the protein-protein interaction (PPI) of these differential expression genes (DEGs) was visualized using Cytoscape with the search tool for the retrieval of interacting genes (STRING). The hub genes in the PPI network were chosen for further investigation.

RESULTS

We identified 65 up-regulated and 190 down- regulated DEGs and the GO enrichment analysis revealed that these DEGs were enriched in biological process related to tumorigenesis and stemness, including alter the extracellular matrix's physicochemical properties, cytoskeletal reorganisation, adhesion, motility, migration, growth, and survival. The Reactome analysis indicated that these DEGs were also involved in modulating function of ECM, regulation cancer metabolism and angiogenesis, tumor growth, proliferation, and metastasis.

CONCLUSION

Our bioinformatic study revealed that FYN, INADL, OCLN, F11R, and TOP2A were potential biomarker panel of BCSCs from secretome.

摘要

背景

乳腺癌干细胞(BCSCs)在高耐药率、复发和转移中起作用。BCSCs 的精确生物标志物可有效协助识别癌症、评估预后、诊断和监测治疗。本研究旨在对 BCSCs 的特定生物标志物进行全面分析。

方法

我们在这项工作中汇总了谱数据集,以揭示 BCSCs 中关键基因和通路的潜在机制。我们从基因表达综合数据库(GEO)中获得了两个微阵列数据集(GSE7513 和 GSE7515),以鉴定 BCSC 中的生物标志物。Enrichr 用于进行功能分析,包括基因本体论(GO)和反应通路。此外,使用 Cytoscape 与搜索工具 for the retrieval of interacting genes(STRING)可视化这些差异表达基因(DEGs)的蛋白质-蛋白质相互作用(PPI)。选择 PPI 网络中的枢纽基因进行进一步研究。

结果

我们鉴定了 65 个上调和 190 个下调的 DEGs,GO 富集分析显示这些 DEGs富集于与肿瘤发生和干细胞特性相关的生物学过程,包括改变细胞外基质的物理化学特性、细胞骨架重组、黏附、运动、迁移、生长和存活。Reactome 分析表明,这些 DEGs还参与调节 ECM 的功能、调节癌症代谢和血管生成、肿瘤生长、增殖和转移。

结论

我们的生物信息学研究表明,FYN、INADL、OCLN、F11R 和 TOP2A 可能是 BCSC 分泌组中的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5125/11318819/646a932fa9df/APJCP-25-1803-g001.jpg

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