Microarray analysis of differentially expressed miRNA in triple negative breast cancer: A study of western India

Background: Triple-negative breast cancer (TNBC) is a genetically and morphologically heterogeneous group with aggressive biological behaviour and specific response to therapy. It accounts for 15–20% of all breast cancers and has two subtypes: basal like and non-basal like. MicroRNAs, which regulate gene expression, play a role in TNBC, potentially acting as oncogenes or tumor suppressors. Objective: Identification of differentially expressed miRNA of potential clinical relevance in TNBC patients. Methods: In this study, miRNA profiling by microarray was performed in tumor tissues of 86 patients with TNBC and 12 healthy individual. Further, the clinical relevance of differentially expressed miRNA was evaluated. Results: In TNBC, 2410 differentially expressed miRNAs were identified and of them 98% were down-regulated, while only 2% were up-regulated. Up regulation of 55 miRNA was observed which target 16 genes. Top 5 genes identified were CDNK1A, p53, TGFB1, APC and HRAS. Of 7 ranking methods, 5 ranking method identified TGFB1 as most significant hub gene. Up regulated miRNA expression then compared between patients who undergone remission and patients who developed disease relapse and only miR-4532 was found upregulated in patients with disease relapse. Further, up regulation of miR-4532 showed a trend of reduced disease-free and overall survival. The down-regulated miRNAs target 238 genes involved in TNBC pathogenesis and progression. The top five hub genes were CDH1, PTEN, MYC, STAT3, and VEGFA. Of 7 ranking methods, 5 ranking method identified STAT3 as most significant hub gene. This study identified 32 novel miRNAs playing a tumor suppressive role and found down-regulated in TNBC. Among these two novel miRNAs, miR-1273g-3p and miR-4459 were found expressed in all TNBC patients. Patients with down-regulation of these miRNAs showed significantly reduced disease-free and overall survival. The ROC curve analysis indicated that miR-4532 and miR-4459 were successful in distinguishing TNBC patients from healthy controls. Conclusion: Our data identified that up regulation of miR-4532 and down regulation of miR-4459 might have the potential to be used as both diagnostic and prognostic biomarker in TNBC.