MicroRNA-126 Expression in the Peripheral White Blood Cells of Patients with Breast and Ovarian Cancer is a Potential Biomarker for the Early Prediction of Cancer Risk in the Carriers of Methylated

Constitutive breast cancer type 1 gene () promoter methylation is associated with increased cancer risk, but its role in cancer-free (CF) female carriers is incompletely understood. MicroRNA (miR) is modulated during early tumorigenesis. The present study assessed the modulation of miR-126 expression in the peripheral white blood cells (WBC) of patients with breast cancer (BC) and ovarian cancer (OC) as a biomarker of cancer risk in methylation carriers. A total of 1,114 female subjects [502 patients with BC, 187 patients with OC and 425 CF volunteers] were involved. Screening for promoter methylation in WBC was performed using the methylation-specific polymerase chain reaction (PCR) assay, mRNA was analyzed using a reverse transcription-quantitative PCR assay and miR-126 expression was analyzed using a stem-loop RT-qPCR assay. WBC promoter methylation status was significantly associated with OC (P=0.0266), early-onset BC (P=0.0003) and triple-negative BC (P=0.0066). Notably, 9.4% of the CF group exhibited WBC promoter methylation. In addition, high levels of miR-126 in WBCs were detected in all three groups. The increased level of miR-126 was significantly associated with a lower risk of distant metastasis (P=0.045) in BC, but a higher risk of disease progression and death (P=0.0029) in OC. There was a positive correlation between mRNA and miR-126 levels in the WBCs of all three groups, regardless of promoter methylation status. Notably, circulating miR-126 level was decreased in the BC and OC groups, but not in the CF group. Together, these results suggest the likely involvement of miR-126 in the constitutional methylation of promoter-related malignancies. Therefore, miR-126 may be a candidate biomarker for the early prediction of BC and OC risk in CF methylation carriers.