Tamoxifen sensitivity-related microRNA-342 is a useful biomarker for breast cancer survival

Abstract

MicroRNAs (miRNAs) have emerged as one of the crucial regulators of cancer progression. Some miRNAs are reported to be related to the response of breast cancer to tamoxifen (TAM). In this study, we investigated whether the levels of TAM response-related miRNAs translate to patient survival. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used and Gene Set Enrichment Analysis (GSEA) was performed. Four TAM response-related miRNAs, miR-221, miR-222, miR-342, and miR-451, were identified by literature search. Patients with high expression of miR-342, related to TAM sensitivity, were associated with better survival in TCGA cohort (Overall Survival (OS), p=0.02; Disease Free Survival (DFS), p=0.03, respectively), and in two other independent GEO cohorts (OS, p=0.02 and p=0.0007, respectively). High expression of miR-342 was associated with significantly better survival in ER-positive patients (p=0.04), but not in ER-negative or triple-negative patients. Surprisingly, high expression of miR-451, reported to increase the sensitivity to TAM, was associated with worse survival (p=0.002). MiR-221 and miR-222 did not show any significance in survival. Lastly, GSEA demonstrated that lower miR-342 expression was significantly associated with the enrichment of TAM resistance-related gene expression, and higher miR-342 expression with TAM sensitivity-related gene expression, but miR-221, miR-222 and miR-451 were not. For the first time, we used “big data” from TCGA and GEO cohorts to analyze multiple miRNAs with respect to survival impact and TAM sensitivities. We demonstrated that TAM sensitivity-related miR-342 could be a promising biomarker, especially in luminal type breast cancer patients.