Different levels of serum microRNAs in prostate cancer and benign prostatic hyperplasia: evaluation of potential diagnostic and prognostic role

Abstract

IntroductionDiagnosis of prostate cancer (PCa) is based on prostate biopsy that is performed when prostate specific antigen (PSA) is persistently altered over time and/or abnormal digital rectal examination is found. Serum PSA levels increase in both PCa and benign prostatic hyperplasia, leading to an increased number of unnecessary biopsies. There is an urgent need to unravel PCa-specific molecular signatures.Patients and methodsThis study aimed at characterizing a panel of circulating micro RNAs (miRNAs) that could distinguish PCa from benign prostatic hyperplasia in a population of age-matched patients with increased PSA levels. Both miRNAs targeting genes involved in PCa onset and miRNAs whose role in PCa has been highlighted in other studies were included. For this purpose, let-7c, let-7e, let-7i, miR-26a-5p, miR-26b-5p, miR-24-3p, miR-23b-3p, miR-27-b-3p, miR-106a-5p, miR-20b-5p, miR-18b-5p, miR-19b-2-5p, miR-363-3p, miR-497, miR-195, miR-25-3p, miR-30c-5p, miR-622, miR-874-3p, miR-346 and miR-940 were assayed through real-time PCR in 64 patients with PCa and compared with 60 patients with benign prostatic hyperplasia. The ability of miRNAs to predict the stage of disease was also analyzed.ResultsLet-7c, let-7e, let-7i, miR-26a-5p, miR-26b-5p, miR-18b-5p and miR-25-3p were able to discriminate patients with PCa from those harboring benign prostatic hyperplasia, both presenting altered PSA levels (>3 ng/mL). MiR-25-3p and miR-18b-5p showed the highest sensitivity and specificity to predict PCa, respectively. The combination of these two miRNAs improved the overall sensitivity. A correlation between pathological Gleason score and miRNA expression levels was reported; miR-363-3p, miR-26a-5p, miR-26b-5p, miR-106a-5p, miR-18b-5p, miR-25-3p and let-7i decreased in expression concomitantly with an increase in malignancy.ConclusionThis study confirms serum miRNAs to be reliable candidates for the development of minimally invasive biomarkers for the diagnosis and prognosis of PCa, particularly in those cases where PSA acts as a flawed marker.

Candidate diagnostic miRNAs that can detect cancer in prostate biopsy

“…Many of them were identified by high‐throughput technologies and subsequently validated by standard PCR‐based methods; however, limited overlap has been observed among these findings. According to recently published studies, the most promising molecules for diagnosis and prognosis of PCa are miR‐1, miR‐18b‐5p, miR‐21, miR‐106b, miRNA‐141, miRNA‐145, miR‐182‐5p, miR‐200b‐3p, miRNA‐205, miRNA‐221, and miR‐375 . In the present study, only four miRNAs appeared to differentiate between non‐malignant and malignant prostate pathology, and there were only 17 in common among the 110 miRNAs reported here and 69 miRNAs reported by one of the largest and most comprehensive miRNA expression profiling studies of PCa to date .…”

The role of microRNAs in prostate cancer migration, invasion, and metastasis

“…Typically Let‐7c, let‐7e, let‐7i, miR‐26a‐5p, miR‐26b‐5p, miR‐18b‐5p, and miR‐25‐3p are confirmed miRNAs as discriminative tools (Cochetti et al, ).…”

Low expression of microRNA-30c promotes prostate cancer cells invasion involved in downregulation of KRAS protein

“…Ambs et al (7) studied the differences in miRNA and mRNA in 60 cases of prostate cancer and normal prostate tissue and revealed that miRNA is associated with the development of prostate cancer, and miRNA controls tumor growth by regulating the expression of tumor-associated genes to promote prostate cancer occurrence and development. Chen et al (8) and other comparative studies (9,10) of the expression of miRNA in the plasma of patients with prostate cancer and benign prostatic hyperplasia revealed that the expression of miR-622 and miR-1285 significantly increased, while the expression of let-7e, Let-7c and miR-30c significantly decreased. Therefore, the present study hypothesized that the differential expression of the 5 miRNAs in the plasma may be used as a biochemical marker and, combined with the prostate-specific antigen test, can be used in the diagnosis of prostate cancer.…”