MicroRNA profiling in prostate cancer--the diagnostic potential of urinary miR-205 and miR-214.

Prostate cancer (PCa) is the most common type of cancer in men in the United States, which disproportionately affects African American descents. While metastasis is the most common cause of death among PCa patients, no specific markers have been assigned to severity and ethnic biasness of the disease. MicroRNAs represent a promising new class of biomarkers owing to their inherent stability and resilience. In the present study, we investigated potential miRNAs that can be used as biomarkers and/or therapeutic targets and can provide insight into the severity and ethnic biasness of PCa. PCR array was performed in FFPE PCa tissues (5 Caucasian American and 5 African American) and selected differentially expressed miRNAs were validated by qRT-PCR, in 40 (15 CA and 25 AA) paired PCa and adjacent normal tissues. Significantly deregulated miRNAs were also analyzed in urine samples to explore their potential as non-invasive biomarker for PCa. Out of 8 miRNAs selected for validation from PCR array data, miR-205 (p<0.0001), mir-214 (p<0.0001), miR-221(p<0.001) and miR-99b (p<0.0001) were significantly downregulated in PCa tissues. ROC curve shows that all four miRNAs successfully discriminated between PCa and adjacent normal tissues. MiR-99b showed significant down regulation (p<0.01) in AA PCa tissues as compared to CA PCa tissues and might be related to the aggressiveness associated with AA population. In urine, miR-205 (p<0.05) and miR-214 (p<0.05) were significantly downregulated in PCa patients and can discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity. In conclusion, present study showed that miR-205 and miR-214 are downregulated in PCa and may serve as potential non-invasive molecular biomarker for PCa

Comparison of miRNA expression on the basis of ethnicity.

<p>Box plots represent the fold difference in expression levels of four miRNAs in PCa tissues as compared to their normal adjacent counterpart. Data for 15 Caucasian American (CA) and 25 African American (AA) patients as assessed by qRT-PCR is shown. Expression levels of the miRNAs were normalized to U6 snRNA as endogenous control. Statistically significant differences were determined using unpaired Student’s T-test.</p

Clinical-pathological characteristics of the prostate cancer patients.

<p>Clinical-pathological characteristics of the prostate cancer patients.</p

Demographic and clinico-pathological characteristics of the participants for urine samples.

<p>Demographic and clinico-pathological characteristics of the participants for urine samples.</p

Pathway network of the genes targeted by differentially modulated miRNAs.

<p>Pathway network was constructed for commonly predicted target mRNAs of differentially modulated miRNAs (miR-205, miR-214, miR-221 and miR99b), by using Pathway Studio 9.0 (A) Commonly predicted miRNA targets with common regulators. (B) Directly interacting targets.</p

Differentially expressed miRNAs in Prostate Cancer Tissues.

*<p>miRNAs selected for tissue validation.</p

Prognostic accuracy of miR-205 and miR-214 in urine samples.

<p>The quantification of miR-205 and miR-214 together can enhance the diagnostic value and can be used to discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity.</p