The association of let-7c, miR-21, miR-145, miR-182, and miR-221 with clinicopathologic parameters of prostate cancer in patients diagnosed with low-risk disease

Abstract

Background: The diagnostic benefit of prostate specific antigen (PSA) is limited, owing to its lack of specificity, particularly in men with PSA levels of 4.0 to 10.0 ng/mL. Therefore, there is a need for more specific and sensitive biomarkers to improve diagnostic accuracy and to predict prostate cancer (PCa) progression. Assessing the expression levels of specific microRNAs (miRNAs) in patients with PCa may be helpful in detecting cancer and predicting the cancer prognosis and its evolution, and may serve as markers to decide the treatment. We examined the expression levels of five miRNAs (let-7c, miR-21, miR-145, miR-185, and miR-221) on patients with low-risk PCa who had been eligible for active surveillance but underwent radical prostatectomy. We investigated the correlation between the relative expression of miRNAs and clinicopathologic parameters to evaluate their clinical significance.

Materials and methods: Total RNA was isolated from the tumor and the corresponding non-neoplastic prostate tissue of 45 patients who underwent radical prostatectomy. Quantitative reverse transcriptase-polymerase chain reaction was used to measure the levels of let-7c, miR-21, miR-145, miR-185, miR-221, and RNU6B expression, using TaqMan MicroRNA Assays. miRNA expression was examined in low-risk PCa, and miRNAs' association with Gleason upgraded (GU) and biochemical recurrent (BR) patients was evaluated.

Results: We observed that miR-21 and miR-182 were overexpressed; conversely, let-7c, miR-145, and miR-221 were underexpressed in patients with low-risk PCa. GU patients (n = 16) and non-upgraded patients (n = 28) were compared. miR-145 was downregulated significantly in the GU group (P = 0.03). Similarly, miR-221 was downregulated significantly in patients with BR (n = 14) compared with non-recurrent patients (n = 30) (P = 0.04). Receiver operator characteristics (ROC) curve analysis revealed that miR-221 levels were significantly associated with BR in patients with a cut-off <-1.666, a value at which sensitivity was 70% and specificity 71% (area under curve [AUC] = 0.705, P = 0.030).

Conclusions: There is still a need for a tumor marker with higher sensitivity and specificity than that of PSA. Among the five miRNAs examined, miR-221 was most associated with biochemical recurrence in low-risk PCa.

Keywords: PSA; low-risk PCa; miRNA; microRNA; prostate cancer.