Increased oncogenic microRNA-18a expression in the peripheral blood of patients with prostate cancer: A potential novel non-invasive biomarker

Abstract

MicroRNAs have been demonstrated to be stably detectable in peripheral blood, thus representing important sources of non-invasive biomarkers of various diseases, including cancer. Recently, microRNA-18a (miR-18a) has been revealed to be highly expressed in prostate cancer (PC) tissues, acting as an oncogenic miRNA. The present study evaluated miR-18a expression in the peripheral blood of patients with PC, patients with benign prostatic hyperplasia (BPH), and healthy individuals, to assess the feasibility of using peripheral blood miR-18a as a potential non-invasive biomarker for PC. Total RNA was extracted from peripheral whole blood samples from 24 PC patients, 24 BPH patients and 23 healthy control individuals. The expression of miR-18a was assessed by reverse transcription quantitative polymerase chain reaction. The results revealed that miR-18a expression was significantly higher in PC patients than in BPH patients and healthy controls [fold change (mean ± standard deviation), 5.5±1.4 for PC, 1.5±0.5 for BPH and 1.2±0.6 for controls; P<0.005]. Higher miR-18a expression was strongly associated with PC [odds ratio (OR), 4.602; 95% confidence interval (CI), 2.194-9.654; P=0.001], but was not significantly associated with BPH (OR, 1.2; 95% CI, 0.7-2.02; P=0.332). Despite the small number of patients, which limits the statistical power of the study, higher miR-18a expression was observed to be significantly correlated with certain clinicopathological parameters, including Gleason score >7 and pathological tumor stage 3/4 (P<0.005). A receiver operating characteristic (ROC) analysis revealed that miR-18a discriminated PC patients from BPH patients and healthy controls [area under the curve (AUC), 0.805; 95% CI, 0.704-0.906). Furthermore, use of the ROC curve to discriminate PC from BPH patients yielded an AUC of 0.878 (95% CI, 0.783-0.972). In summary, the present results indicate that miR-18a expression is significantly increased in peripheral blood of patients with PC compared with that of BPH patients and healthy individuals, and that higher miR-18a expression is associated with progression of PC. Peripheral blood oncogenic miR-18a may serve as a potential novel non-invasive biomarker for PC that also facilitates discrimination between PC and BPH.

Keywords: benign prostatic hyperplasia; biomarker; microRNA; peripheral blood miR-18; prostate cancer.

Figure 1.

miR-18a expression in peripheral blood of PC patients, BPH patients and healthy individuals. The expression of miR-18a relative to that of U6 small nuclear RNA was determined by quantitative polymerase chain reaction in peripheral blood samples from PC patients (n=24), BPH patients (n=24) and healthy control individuals (n=23). Data are presented as the mean ± standard deviation. *P<0.05 vs. BPH patients and controls. miR-18a, microRNA-18a; PC, prostate cancer; BPH, benign prostatic hyperplasia.

Figure 2.

Association between pathological parameters and miR-18a expression in peripheral blood of prostate cancer patients. (A) Relative miR-18a expression in patients with Gs <7 (n=5), Gs =7 (n=10) and Gs >7 (n=9) (*P<0.05 vs. Gs =7 and <7). (B) Relative miR-18a expression in patients of stage pT1/2 (n=14) and pT3/4 (n=10) (*P<0.05 vs. pT1/2). miR-18a expression was measured relative to U6 small nuclear RNA using quantitative polymerase chain reaction, and all data are presented as the mean ± standard deviation. miR-18a, microRNA-18a; Gs, Gleason score; pT, pathological tumor stage.

Figure 3.

ROC curve analysis (A) miR-18a is able to distinguish PC patients from BPH patients and healthy control individuals (AUC, 0.864; 95% CI, 0.751–0.977; P<0.001). (B) miR-18a can distinguish PC patients from BPH patients (AUC, 0.878; 95% CI, 0.783–0.972; P<0.001). ROC, receiver operating characteristic; miR-18a, microRNA-18a; PC, prostate cancer; BPH, benign prostatic hyperplasia; AUC, area under the curve; CI, confidence interval.