Abstract 4435: Exosomal miR-3622a as prognostic marker in prostate cancer

Abstract

Abstract Loss of chromosome (chr) 8p21 is a frequent genomic alteration in prostate cancer (PCa). Genomic deletions of this region increase significantly with tumor grade and are associated with tumor progression and poor prognosis. A common region of loss of heterozygosity (LOH) has been mapped to the chr8p21 locus that primarily harbors prostate-specific NKX3.1 homeobox gene. We recently demonstrated that this frequently deleted locus is associated with a cluster of microRNA genes- miR-3622a/b- that are lost in prostate cancer and play an important mechanistic role in PCa progression and metastasis. MicroRNA expression profiling in microdissected human PCa clinical tissues showed that miR-3622a/b expression is widely downregulated and is correlated with poor survival outcome in prostate cancer. Our analyses suggested that miR-3622a has potential as a prognostic and diagnostic marker for prostate cancer. Extending these findings, we explored the prognostic potential of serum miR-3622a in prostate cancer patients. Since exosomes provide an important source of non-invasive, circulating biomarkers and represent an enriched source of microRNAs for biomarker profiling, we profiled the microRNA content of exosomes derived from sera of prostate cancer patients. In a pilot study, we profiled exosomal miRNAs from a training cohort of individuals with benign prostate hyperplasia (BPH), an indolent form of PCa or aggressive metastatic PCa. Exosomes were isolated from sera of prostate cancer patients and integrity of exosomal preparations was confirmed by nanoparticle tracking analysis and Western blot analyses for exosomal markers. Expression analyses of exosomal miR-3622a expression showed that this miRNA is enriched in exosomes. Higher levels of miR-3622a were significantly associated with tumor stage and lymph node metastasis in a cohort of prostate cancer clinical specimens. Further, ROC (Receiver Operating Characteristic) analyses showed that exosomal miR-3622a expression can be a single significant parameter to discriminate between BPH and prostate cancer. Overall, our data suggests that exosomal miR-3622a is a promising prognostic biomarker for prostate cancer. patients. Citation Format: Thao Yang, Divya Bhagirath, Kirandeep Sekhon, Nathan Bucay, Shahana Majid, Varahram Shahryari, Marisa Shiina, Yutaka Hashimoto, Priyanka Kulkarni, Pritha Dasgupta, Mitsuho Imai-Sumida, Soichiro Yamamura, Z Laura Tabatabai, Kirsten Greene, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng, Sharanjot Saini. Exosomal miR-3622a as prognostic marker in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4435. doi:10.1158/1538-7445.AM2017-4435