Abstract 3383: Circular RNAs as non-invasive diagnostic biomarkers for prostate cancer
Authors: Shah Palak , Bawa Pushpinder , Xiao Lanbo , Kleyman Yelena , Vo Josh , Dhanasekaran Saravana M. , Brown Jason , Loeding Nicolette , Koons Alexander , Siddiqui Javed , Cao Xuhong , Chinnaiyan Arul M. 
Published: June 2022

Prostate cancer is one of the most common cancers in men. The disease is largely indolent in nature and treatment of low-risk prostate cancer is not always necessary. However, a fraction of the patients will progress to aggressive disease which accounts for most of the cancer related mortality. Detection methods accurately differentiating between high- and low-risk patients for lethal prostate cancer is a critical need and currently, prostate biopsies and subsequent histopathology and molecular profiling are the most definitive way to differentiate between these two patient populations. But biopsies are invasive procedures associated with significant morbidity. Hence, there exists a critical need to develop non-invasive and highly sensitive diagnostic biomarkers to avoid unnecessary biopsies. Here, we propose to develop a novel biomarker panel which constitutes of a class of RNA molecules called circular RNA (circRNA) to be detected in liquid biopsies. Circular RNAs are covalently closed RNA structures, which are resistant to degradation by exoribonucleases because of the absence of free termini in their nucleotide chain. Due to their increased stability compared to their linear counterparts, circRNAs are ideal candidates for biomarkers, especially in non-invasive liquid biopsies. Using MiOncoCirc, a circRNA compendium from &gt;2,000 primary and metastatic cancer tissues representing 40 cancer types, we first identified 9 circRNAs that are specifically expressed in prostate adenocarcinoma (PRAD) compared to all other cancer types. Next, we examined if these candidates are differentially expressed between PRAD and normal prostate tissues. Based on higher levels of expression which were statistically significant in the PRAD compared to normal prostate tissues, we promoted 4 circRNAs to our biomarker panel. In addition, our panel also includes 2 circRNAs that we predicted to arise from PRAD specific lncRNAs. To study the expression of the novel 6-circRNA biomarker expression in high-risk prostate cancer patients we developed a capture-based RNA sequencing assay. For the initial round we used this assay to test our pilot post-DRE patient urine sample EDRN cohort and detected expression of the prostate cancer-specific circRNAs in a subset of these post-DRE urine samples. We are in the process of expanding our test cohort which will also contain additional clinical annotations such as Gleason score. Post cohort assembly we intend to run our 6-circRNA capture assay on these samples to determine whether the expression levels of candidate circRNAs are correlated with disease stage and other clinical parameters. Our results will facilitate the rapid development of a diagnostic test using non-invasive urine samples for the early detection of high-risk prostate cancer.

Citation Format: Palak Shah, Pushpinder Bawa, Lanbo Xiao, Yelena Kleyman, Josh Vo, Saravana M. Dhanasekaran, Jason Brown, Nicolette Loeding, Alexander Koons, Javed Siddiqui, Xuhong Cao, Arul M. Chinnaiyan. Circular RNAs as non-invasive diagnostic biomarkers for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3383.