Differentially expressed miR-20, miR-21, miR-100, miR-125a and miR-146a as a potential biomarker for prostate cancer.

Prostate cancer is the leading cause of death among men worldwide. Deregulation of microRNAs has been reported in many cancers. Expression of microRNAs miR-20a-5p, miR-21-5p, miR-100-5p, miR-125a-5p and miR-146a-5p in tissue blocks of histologically confirmed prostate cancer patients compared with BPH patients, to identify potential microRNA biomarker for prostate cancer. MicroRNA was isolated and expression was quantified by qRT-PCR using Taqman Advanced microRNA assay kits. The interactions between the microRNA:target mRNA were predicted by using bioinformatics tools such as miRwalk and miRTargetlink. The experimentally validated targets were analysed using gprofiler to identify their molecular function, biological process and related pathways. The expression analysis revealed that miR-21 and miR-100 were significantly down-regulated whereas miR-125a was up-regulated in prostate cancer patients. Comparative analysis of the expression levels with tumor grading reveal that miR-100 was significantly down-regulated (p < 0.05) in high grade tumor, indicating that miR-100 associated with prostate cancer. ROC analysis revealed that combined analysis of down-regulated miRNAs (miR-21 and miR-100) shown AUC of 0.72 (95% CI 0.65-0.79). The combined analysis of all five miRNAs showed AUC of 0.87 (95% CI 0.81-0.92). The targets prediction analysis revealed several validated targets including BCL2, ROCK1, EGFR, PTEN, MTOR, NAIF1 and VEGFA. Our results provide evidence that combined analysis of all the five miRNAs as a panel can significantly improve the prediction level of the presence of prostate cancer and may be used as a potential diagnostic biomarker.

Study on the SFRP4 gene polymorphism and expression in prostate cancer.

Prostate cancer is a heterogeneous disease and considered to be the most commonly diagnosed cancer. SFRP4 gene acts as Wnt antagonist in the Wnt signalling pathway, thereby playing an important role in carcinogenesis. The aim of the present study was to investigate two single-nucleotide polymorphisms: c.958 C>A (rs1802073) and c.1019 G>A (rs1802074) in the SFRP4 gene and its expression in prostate cancer. A sample size of 100 cases and 100 age-matched controls were recruited for the study. Statistical analysis revealed the heterozygous GA genotype of rs1802074 significantly increased in cases when compared to controls. Analysis of sFRP4 expression based on the genotypes showed a significantly increased expression for the heterozygous GA and homozygous AA genotypes in cases when compared to the controls. Fold change was calculated using 2-ΔΔCT method and the results showed that there were a 3.4 and 4.5 fold increase in the sFRP4 expression for GA and AA genotypes, respectively. Our results suggest that the rs1802074 polymorphism in SFRP4 gene may be associated with the risk of prostate cancer.

Genetic Polymorphisms in miR-146a, miR-196a2 and miR-125a Genes and its Association in Prostate Cancer.

The increase in incidence of prostate cancer in the Indian Population stresses the need to identify genetic markers for susceptibility and prognosis. Recent studies show that microRNAs play an important role in tumorigenesis by altering proliferation, differentiation and cell death. Gene polymorphisms not only in promoter region but also within miRNA gene have been shown to affect expression. The present study was aimed to analyze the role of miR-146a, miR-196a2 and miR-125a gene polymorphisms in prostate cancer. Genotyping of three SNPs rs73318382, rs57095329, rs2910164 in miRNA146a, rs11614913 in miR-196a2 and rs41275794, rs12976445, rs10404453 and rs1297533 in miR-125a was performed in 100 cases and 100 controls. Statistical analysis revealed the heterozygous AG genotype of the rs57095329 was significantly decreased in the cases when compared to the controls (OR-0.45, CI -0.24 to 0.85, p value-0.02) indicating an inverse association of this genotype with prostate cancer. Further the heterozygous CT of miR-196a2 (rs11614913) (OR-1.88, CI-1.06 to 3.35, p-0.02) and homozygous CC of miR-125a (rs12976445) (OR-2.55, CI -1.15 to 4.65, p-0.03) showed increased risk for prostate cancer. Combined analysis of all the genotypes revealed that the haplotype combination AGGCGTGG (OR = 0.09 at CI 95% (0.01-0.65) showed an inverse association with prostate cancer. Stratified analysis based on the age and tumor grade revealed no significant association.