miRNAs Regulating GSTP1 as Potential Diagnostic Biomarkers in Prostate Cancer.

Abstract

Background: Specific and sensitive minimally-invasive biomarker(s) for early detection of prostate cancer is urgently needed to reduce false detection and odds of overtreatment. MicroRNAs (miRNAs) are 19-24-nt noncoding RNAs that regulate gene expression, have emerged as promising blood-based biomarkers due to their frequent dysregulation in cancer.

Methods: miRNA levels were quantified in a total of 86 human plasma samples, consisting of 44 prostate cancer patients and 42 individuals with no cancer, using quantitative real-time PCR. Serum PSA and plasma GSTP1 levels were detected by using ELISA assay. The sensitivity and specificity of these miRNAs were evaluated through ROC (Receiver Operating Characteristic) curve analysis.

Results: To identify sensitive and specific miRNA biomarkers for prostate cancer, target prediction analysis was performed. This analysis highlighted hsa-miR-133a-3p, hsa-miR-144-3p, hsa-miR-153-3p, and hsa-miR-590, which regulate glutathione S-transferase P1 (GSTP1), a gene epigenetically silenced in all stages of prostate cancer. The absolute expression levels of these miRNAs were quantified in plasma samples from 44 prostate cancer patients and 42 noncancer individuals. Sensitivity and specificity were assessed using ROC curve analysis. Binary logistic regression ROC analysis revealed that hsa-miR-133a-3p and hsa-miR-153-3p demonstrated exceptional specificity and sensitivity for prostate cancer detection, with p values of < 0.0001 and 0.0003, outperforming PSA levels. Further validation in an independent data set of 64 noncancer individuals and 26 prostate cancer patients confirmed significant differences in hsa-miR-133a-3p and hsa-miR-153-3p expression between the groups. The two-miRNA panel exhibited high diagnostic accuracy, with an area under the curve between 0.98 and 1.0.

Conclusions: These results suggest that the two-miRNA panel represents a significant advancement over PSA testing and shows strong potential as a reliable blood-based diagnostic tool for prostate cancer detection.