Identification of Extra Cellular Matrix (ECM) Genes in Triple Negative Breast Cancer

Abstract

Introduction: Extracellular Matrix (ECM) is often abnormally produced, degraded, and remodelled, which creates a pro-tumorigenic environment in cancer and leads to tumor growth, angiogenesis, invasion and metastasis. This study aimed to investigate ECM genes by microarray-based transcriptome analysis and miRNA that target ECM genes in triple-negative breast cancer (TNBC).

Materials and Methods: The current study evaluated 682 TME-related genes using Array Comparative Genomic Hybridization (aCGH) in 55 patients with TNBC.

Results: 266 ECM genes were studied by transcriptome analysis, and it was observed that 132 ECM genes were up-regulated and 25 ECM genes were down-regulated in TNBC. Regarding upregulated genes, the majority of the genes were of Collagen family genes. Regarding downregulated genes, 14 genes were of Integrin family genes. PPI network analysis of upregulated genes using the STRING database, five hub genes identified were FN1, COL3A1, COL1A2, COL1A1, and COL6A2. Five of eight ranking methods identified FN1 and COL1A1 as the top most upregulated hub genes. The top 5 significant down-regulated hub genes were ITGB2, ITGAM, ITGAX, ITGB3, and ITGA4. Of 8 ranking methods, 7 ranking methods identified ITGB2, ITGAM and ITGAX as the most significant down-regulated hub genes. Further, target gene - miRNA regulatory networks using the miRTargetLink 2.0 tool.

Conclusion: ECM genes FN1, COL1A1, ITGB2, ITGAM and ITGAX may be involved in disease progression in TNBC and, after validation, may be considered therapeutic targets for TNBC