Discovery and Validation of Serum MicroRNAs as Early Diagnostic Biomarkers for Prostate Cancer in Chinese Population

Abstract

Prostate cancer (PCa) incidence has been rising in Chinese population. Current PSA-based biopsy has limited positive rate. Our research focused on development of serum markers for the diagnosis of PCa in patients with elevated PSA. miRNAs are found to be aberrantly expressed in many types of cancer. They are readily detectable in plasma and serum. Currently, miRNAs are being evaluated as potential prognostic and diagnostic tools for many types of cancer. We first profiled global serum miRNAs in a pilot set of PCa and benign prostatic hyperplasia (BPH) cases undergoing TRUS-guided prostate biopsy due to elevated PSA levels. A total of 20 differentially expressed miRNAs were discovered by high throughput microarray for further testing using qRT-PCR. In the training phase with 78 PCa and 77 BPH cases, miR-365a-3p, miR-4286, miR-424-5p, miR-27a-3p, and miR-29b-3p were found to have potential diagnostic value. The Logistics regression equation was established by 5 parameters including PSA, prostate volume, miR-4286, miR-27a-3p, and miR-29b-3p and ROC analysis of this model was made with AUC up to 0.892 (95% CI: 0.832-0.937, sensitivity 78.95%, and specificity 92.21%). The panel had excellent diagnostic performance and its significance was confirmed in 100 serum samples in the validation cohort. Overall, we found a panel of serum microRNAs that have considerable clinical significance in detecting early-stage prostate cancer. When combined with PSA and prostate volume, these microRNAs exhibit favorable diagnostic potency.

The sensitivity and specificity of the total prostate specific antigen test in prostate cancer screening: A Short report

“…This observation was also reported by other studies [10,17]. The threshold or best cut-off value was higher than what other authors reported [11,18]. This could be explained by the observation that men of Black African ancestry have been shown to have higher levels of PSA than Asian or Caucasian due to differences in androgenic and genetic in uences [21] Using a cut of the value of 5.0 ng/ml, TPSA showed a false positive rate as high as 88% and speci city as low as 12.0%, although the sensitivity was 100%.…”

“…Further evidence of the association between PSA and PCa was shown by a signi cant increase in ageadjusted odds ratios with increasing TPSA levels, similar to the ndings by Nakamura, Scorilas [17] and Lyu, Zhao [18].…”

miRNAs as Therapeutic Tools and Biomarkers for Prostate Cancer

“…A panel of 5 parameters including PSA, prostate volume, and serum levels of miR-4286, miR-27a-3p, and miR29b-3p was considered by Lyu et al [ 158 ]. The panel was compared in PCa ( n = 78) and BPH ( n = 77) patients and revealed excellent diagnostic performance in separating the two populations (AUC 0.892, 95% CI: 0.832–0.937, sensitivity 78.95%, and specificity 92.21%) as well as in recognizing the early-stage disease.…”

<p>Role of miRNA-424 in Cancers</p>

“…24,25 It can be detected by miR-424 combined with PSA value and prostate volume to assist in the diagnosis of prostate cancer in patients with elevated PSA. 26 In addition to studies on endocrine organs, the association between miRNAs and digestive system tumors has also been explored. The overall survival rate of pancreatic adenocarcinoma (PAAD) is associated with miRNAs including miR-424, which may have the potential to become a prognostic biomarker for PAAD.…”