MicroRNA Expression Changes in Women with Breast Cancer Stratified by DNA Repair Capacity Levels.

Abstract

Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide and is the leading cause of death among Hispanic women. Previous studies have shown that women with a low DNA repair capacity (DRC), measured through the nucleotide excision repair (NER) pathway, have an increased BC risk. Moreover, we previously reported an association between DRC levels and the expression of the microRNA (miRNA) let-7b in BC patients. MiRNAs can induce genomic instability by affecting the cell's DNA damage response while influencing the cancer pathobiology. The aim of this pilot study is to identify plasma miRNAs related to variations in DRC levels in BC cases. Hypothesis. Our hypothesis consists in testing whether DRC levels can be correlated with miRNA expression levels. Methods. Plasma samples were selected from 56 (27 cases and 29 controls) women recruited as part of our BC cohort. DRC values were measured in lymphocytes using the host-cell reactivation assay. The samples were divided into two categories: low (≤3.8%) and high (>3.8%) DRC levels. MiRNAs were extracted to perform an expression profile analysis. Results. Forty miRNAs were identified to be BC-related (p<0.05, MW), while 18 miRNAs were found to be differentially expressed among BC cases and controls with high and low DRC levels (p<0.05, KW). Among these candidates are miR-299-5p, miR-29b-3p, miR-302c-3p, miR-373-3p, miR-636, miR-331-5p, and miR-597-5p. Correlation analyses revealed that 4 miRNAs were negatively correlated within BC cases with low DRC (p<0.05, Spearman's correlation). Results from multivariate analyses revealed that the clinicopathological characteristics may not have a direct effect on specific miRNA expression. Conclusion. This pilot study provides evidence of four miRNAs that are negatively regulated in BC cases with low DRC levels. Additional studies are needed in order to have a complete framework regarding the overall DRC levels, miRNA expression profiles, and tumor characteristics.