Abstract 2422: Circulating miRNAs as potential biomarkers in prostate cancer pathogenesis.

Abstract

Abstract Introduction: According to the American Cancer Society, prostate cancer (PCa) is a major health concern for U.S. men and is expected to result in approximately 241,740 new cases and about 28,170 deaths in 2012. African American (AA) men have a 60 percent higher incidence rate and twice the death rate of Caucasian men (CA). Whereas metastasis is the most common cause of death, no specific markers have been assigned to the severity and ethnic biasness of the disease. Deregulation of miRNAs has been observed in various human tumors which emphasize their role in cancer pathogenesis, progression and metastasis. This study was aimed to investigate potential miRNAs involved in PCa. The study also aims to identify potential biomarkers and/or their therapeutic targets which can provide insight into the severity and ethnic biasness of disease. Methods: Study was divided into three phases: (I) Candidate serum miRNAs were detected by using PCR microarray (learning set of 6 AA and 6 CA PCa patients). (II) Discriminating performance of candidate miRNAs were validated by real-time RT-PCR in serum [AA (20 PCa patients and 16 controls) and CA (16 PCa patients and 16 controls). (III) Functional studies on candidate miRNA(s) were subsequently performed using gain-and loss-of-function approach in cellular assays. Results: In the discovery phase we obtained 5 miRNAs which were differentially expressed in the AA prostate cancer patients. After careful examination miR-212 and few others were selected for future validation. In the validation set there was an overall high expression of miR-212 in serum of PCa patients as compared to normal individuals (p=0.0110). Subdivision on the basis of ethnicity showed serum expression levels of miR-212 in AA were significantly modulated (p=0.034) as compared to CA PCa patients. Functional validation of miR-212 was done in PC3 and LnCap cell lines. Conclusion: Our results showed a potential role for miR-212 in the regulation of gene expression which in turn can define the aggressiveness associated in African American PCa patients. Citation Format: Anvesha Srivastava, Malathi Ramalinga, Deepak Kumar, Alexander Dimtchev, Juliet Chijioke, Offie Soldin, Xin Li, Catalin Marian, Simeng Suy, Sean P. Collins, Deepak Kumar. Circulating miRNAs as potential biomarkers in prostate cancer pathogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2422. doi:10.1158/1538-7445.AM2013-2422