Plasma circular RNA panel acts as a novel diagnostic biomarker for colorectal cancer

Abstract

BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide, and emerging lines of evidence have implicated circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, in CRC development. However, whether plasma circRNAs might be novel diagnostic biomarkers for CRC remains unclear. MethodsWe investigated the plasma levels of selected circRNAs by quantitative real-time PCR (qRT-PCR). The presence of the candidate circRNAs was confirmed through RNase R assays, qRT-PCR and DNA sequencing, and their diagnostic value was evaluated using a receiver operating characteristic (ROC) curve. ResultsThe plasma levels of three circRNAs (circ-CCDC66, circ-ABCC1 and circ-STIL) were significantly decreased in CRC patients (n = 45) compared with healthy controls (n = 61). The ROC curve analysis showed that the area under the ROC curve (AUC) of the three-circRNA panel was 0.780, which is higher than that of traditional protein biomarkers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19-9). Combining the circRNA panel with CEA and CA19-9 might improve the ability to diagnose CRC (AUC = 0.855). In addition, the plasma circ-ABCC1 level was related to tumor growth and progression, and the plasma circ-CCDC66 and circ-ABCC1 levels were decreased in precursor lesions of CRC, including colon adenomas and adenomatous polyps. More importantly, circ-CCDC66 and circ-STIL were found to be useful for diagnosing early-stage CRC, and the three-circRNA panel improved the ability to diagnose CEA-negative and CA19-9-negative CRC. ConclusionOur study provides the first identification of a panel of three plasma circRNAs that could serve as a novel and independent diagnostic biomarker for CRC.