Circular RNA Expression Signatures Provide Promising Diagnostic and Therapeutic Biomarkers for Chronic Lymphocytic Leukemia

SIMPLE SUMMARY: This study aimed to evaluate the potential of circular RNA (circRNA) expression profiles for the early detection of chronic lymphocytic leukemia (CLL) using bioinformatic algorithms on verified CLL patient datasets. We analyzed and validated the diagnostic performance of circRNAs as potential biomarkers in different CLL sample sets, which reveal better prognostic value than existing clinical risk scales for the prediction of 5-year overall survival. The identification of specific circRNAs from our biomarker panel are also involved in cancer-related pathways, which possess druggable targets for therapeutic interests. Our findings therefore suggest that circRNA signatures represent significant biomarkers for the early detection and surveillance of CLL in addition to providing pharmacogenomic value to personalized medicine. ABSTRACT: Chronic lymphocytic leukemia (CLL) is a known hematologic malignancy associated with a growing incidence and post-treatment relapse. Hence, finding a reliable diagnostic biomarker for CLL is crucial. Circular RNAs (circRNAs) represent a new class of RNA involved in many biological processes and diseases. This study aimed to define a circRNA-based panel for the early diagnosis of CLL. To this point, the list of the most deregulated circRNAs in CLL cell models was retrieved using bioinformatic algorithms and applied to the verified CLL patients’ online datasets as the training cohort (n = 100). The diagnostic performance of potential biomarkers represented in individual and discriminating panels, was then analyzed between CLL Binet stages and validated in individual sample sets I (n = 220) and II (n = 251). We also estimated the 5-year overall survival (OS), introduced the cancer-related signaling pathways regulated by the announced circRNAs, and provided a list of possible therapeutic compounds to control the CLL. These findings show that the detected circRNA biomarkers exhibit better predictive performance compared to current validated clinical risk scales, and are applicable for the early detection and treatment of CLL.