Differential expression of micro-RNAs in breast cancer with relapsed disease: A clinical data base study.

Abstract

e12514 Background: Micro-RNAs (miRNAs) are small, noncoding RNA molecules that play important role in RNA silencing and post-transcriptional regulation of gene expression that are dysregulated in cancer. miRNAs are divided into oncogenic and tumor suppressor miRNAs. Both of these subtypes are known to regulate breast cancer development and progression. We studied the expression of these miRNAs before and after treatment in patients with breast cancer with relapsed disease. Methods: Data was obtained from the TCGA database. 11 patients with biopsy proven diagnosis of invasive ductal adenocarcinoma of the breast receiving adjuvant chemotherapy with relapsed disease who had tissue biopsy post-treatment were included in the study. miRNA expression was assessed in the pre- and post-treatment tissue samples. A total of 178 miRNA were analyzed after filtering out miRNA expression counts < 10. A pair-wise comparison of the differential expression of miRNA before and after treatment with adjuvant chemotherapy was analyzed using a quasi-likelihood F test implemented by bioconductor package, edgeR. This package is well documented for analyzing RNA-seq data due to adjustment for biological variations and measuring error using a negative binomial distribution. The expression of miRNA |Log2FC| > 1 and P value < 0.05 were obtained. Results: Out of 11 female patients, 10 were Caucasian. 9 out of 11 patients’ tumors were Estrogen Receptor positive; 8 patients had progesterone Receptor positive and 1 patient had Human epidermal growth factor receptor2 positive cancer. Of the 178 miRNAs of interest, we found 14 miRNA that are differentially expressed. The miRNA that are up-regulated post-treatment were hsa-miR-148a, hsa-miR-126, hsa-miR-142, hsa-miR-210, hsa-miR-374a, hsa-miR-192. The miRNA that were down-regulated were hsa-miR-197, hsa-miR-155, hsa-miR-149, hsa-miR-365a, hsa-miR-365b, hsa-miR-484, hsa-miR-339 and hsa-miR-3653. Among the miRNA up-regulated post-treatment, miR-148 and miR-126 are known major tumor suppresser miRNA whereas miR-210 and miR-374a are major oncogenic miRNA in breast cancer. Among the miRNA down-regulated post treatment, miR-155 is major oncogenic miRNA whereas miR-365 is major tumor suppressor miRNA in breast cancer. Conclusions: There is mixed expression profile of tumor suppressor miRNA and oncogenic miRNA molecules between before and after treatment in patients with breast cancer with relapsed disease. Further studying these miRNA molecules can help us better understand about the tumor progression and disease relapse.