Correlation Of MiR-195/miR-17-5p With Invasiveness And Prognosis Of Breast Cancer

Objective MicroRNAs (miRNAs) experience effect on tumorproliferation and invasion by various ways. However, the relationship betweenmiRNAs level on formalin-fixed paraffin embedded（FFPE）tissue and their role oninvasiveness and prognosis of breast cancer is not yet clear. At the present study, weaimed to explore the potential of miR-195/miR-17-5p as the new biomarker of breastcancer.Methods The RNA in FFPE of88breast cancer patients with primary tumors wasextracted, and miR-195/miR-17-5p levels were quantified by quantitative real-timepolymerase chain reaction (qRT-PCR). The relationship of miR-195/miR-17-5plevels and clinicopathological variables were assessed by Mann Whitney-U test. RFSand OS survival curves were derived from Kaplan-Meier estimates and the curveswere compared by Log-rank tests. Cox regression analysis was used for multivariateanalysis. All statistical tests were two-sided.Results The levels of miR-195in the breast cancer with histological high grade,tumor size of T3+4, lymph nodal involvement or vessel invasion were significantlydown-regulated, compared with those of patients with histological low grade, tumorsize of T1+2, no lymph node metastasis and vessel invasion (P=0.023, P=0.007,P=0.049, P=0.015, respectively). In addition, no statistically significant difference(P>0.05) was identified between miR-195levels and hormone receptors status,HER2expression, TNM stage, tumor types, recurrence and menstrual status. Whenconsidering2-△Ct=0.270(median level) as cut-off value, Kaplan-Meier survivalanalysis indicated that patients with high miR-195level showed a positiveassociation towards a longer survival, either recurrence-free survival (P=0.014,Log-rank test) or overall survival (P=0.000, Log-rank test). In a multivariate analysis,miR-195expression on FFPE correlated significantly with outcomes of breast cancerand was independent of other prognostic factors.A potential relationship between miR-17-5p levels and existing clinico-pathological parameters of breast cancer, such as menstrual status, tumor size, nodal involvement,stage of disease, hormone receptor status, histological grade, tumor subtype or tumorrelapse was investigated. No statistically significant difference were identified forthese features（P>0.05）. miR-17-5p level was significant lower among HER2negative group than HER2over-expression group（P=0.011）. Lower miR-17-5plevel was seen in breast cancer with tumor vessel invasion compared to patientsabsence of vessel invasion (P=0.000). When considering2-△Ct=0.836(mean level)as cut-off value, no correlation with clinical outcomes were found according tomiR-17-5p expression (high vs. low, P>0.05).Conclusions Our data suggested miR-195expression on FFPE was inverselycorrelated with histological high grade, bigger tumor size, lymph node involvement,vessel invasion. Furthermore, as independent prognostic factor, low miR-195significantly contributes to poor outcomes of breast cancer. Thus miR-195has thepotential as novel predictor of tumor invasiveness and prognostic factor for breastcancer. It suggested that miR-17-5p level is associated with HER2status and vesselinvasion, referring to invasiveness of breast cancer. miR-17-5p level was found to benot correlated with prognosis in breast cancer, which warrants investigation to furtherelucidate.