Abstract
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.
Highlights
Prostate cancer (PCa) is the most frequently diagnosed male cancer and the second-leading cause of oncological mortality in men in the United States [1]
Expression Profiling of miRNAs in Prostate Cancer Tissues Assessing changes in miRNA expression in PCa tissues and biofluids offer a promising tool for identifying specific biomarkers that can aid in the diagnosis and prognosis of PCa
In the present study, using global miRNA profiling followed by validation studies, we showed that miR-205, miR-214, miR-221 and miR-99b were significantly downregulated in PCa tissues as compared to adjacent normal tissue counterparts
Summary
Prostate cancer (PCa) is the most frequently diagnosed male cancer and the second-leading cause of oncological mortality in men in the United States [1]. Owing to its non- specific symptoms and gradual progression, PCa is generally diagnosed at an advanced stage. Performed tests for early detection of PCa include digital rectal examination (DREs) and prostate-specific antigen (PSA) testing. A recent meta-analysis concluded that routine screening with either a DRE or PSA offers no benefit and does not influence PCa mortality [8]. To overcome these drawbacks, additional biomarkers have been proposed including PSA derivatives such as total PSA velocity (total PSAV) and different molecular forms of PSA such as free PSA, BPSA, pro-PSA, and intact PSA [9]. Due to the heterogeneous nature of this disease, additional prognostic biomarkers are urgently needed for better prediction of disease progression that can help in clinical decision making about the timing of biopsy and necessity of treatment
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