MicroRNAs as Potential Liquid Biopsy Biomarker for Patients with Castration-Resistant Prostate Cancer

Nicolas Fernandez,1 Julian Chavarriaga,2 Paola Ayala,3 Adriana Pedraza,4 John Bolivar,5 Juan Guillermo Prada,6 Juan Guillermo Cataño,6 Herney Garcia,7 Juliana Villanueva,6 Daniela Varela,6 Ignacio Zarante3 1Division of Urology Seattle Children’s Hospital, University of Washington, Seattle, WA, USA; 2Division of Urology, Clínica Imbanaco - Quiron Salud, Cali, Colombia; 3Human Genetics Institute, Pontificia Universidad Javeriana, Bogota, Colombia; 4Division of Urology Clínica Desa, Cali, Colombia; 5Division of Urology, Department of Surgery, Hospital Universitario San Ignacio, Bogota, Colombia; 6Division of Urology, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogota, Colombia; 7Division of Urology, Department of Surgery, Universidad del Valle, Cali, ColombiaCorrespondence: Nicolas Fernandez, Division of Urology, Seattle Children’s Hospital, University of Washington, 5801 Sand Point Way NE, Seattle, WA, 98105, USA, Tel +1 206 351 2618, Email nicolas.fernandez@seattlechildrens.orgPurpose: To identify micro-RNAs (miRNAs) expression profiles in peripheral blood plasma that could play a role as potential biomarkers in patients who progressed to castration-resistant prostate cancer (CRPC). Liquid biopsy analysis of miRNAs is a fast-developing field with a considerable likelihood to predict tumor progression and metastasis by targeting genes involved in oncogenesis.Patients and Methods: Differential expression analysis of miRNAs profile in CRPC patients was performed by creating small RNA libraries of circulating miRNAs using HiSeq2500 Illumina platform. A secondary analysis of aligned reads with miRNA identification and quantification was performed using miARmaSeq. Using the Bowtie algorithm, the selected variants were compared to reference nucleotide sequence GRCh38 and miRbase. Novel miRNA sequences were structurally analyzed using mirDeep2®.Results: A total of 16 patients with CRPC were included for analysis. Identified circulating miRNAs were hsa-miR-885-3p, hsa-miR-4467, hsa-miR-4686, hsa-miR-146a-3p, hsa-miR-6514-5p. Genes identified as regulated by these miRNAs were GPR56, BDNF, CTNND1, C17orf62, and DTNA.Conclusion: We explored the miRNA expression profile in patients with CRPC, identifying five miRNAs implicated in the regulation of genes involved in prostate cancer (PCa) oncogenesis and progression. We also found miRNA 855– 3p in peripheral blood for the first time, which has a critical role in tumor growth mechanisms and higher expression profile than in healthy individuals.Keywords: prostatic neoplasm, prostatic neoplasms, castration-resistant, microRNAs, biomarkers, genital neoplasms, male