Abstract B42: A two-lncRNA signature in serous exosomes serves as a new biomarker for colorectal cancer diagnosis

Abstract

Abstract Background: Many studies have shown that long non-coding RNAs (lncRNAs) participate in the initiation and development of colorectal cancer (CRC). We previously reported that lncRNAs can be detected and are stable in serum. Exosomes (EXOs) are small (30 to 100 nm) membrane-bound particles that are released from normal, diseased, and neoplastic cells and are present in blood and other bodily fluids. EXOs contain a variety of molecules including signal peptides, mRNA, microRNA, and lipids. However, it is unclear if lncRNAs in serous EXOs represent a novel marker to detect CRC. Methods: Total RNA and serous EXO RNA were isolated from serum of 60 CRC patients, 60 age- and sex-matched healthy subjects. We measured 39 candidate cancer-associated lncRNAs by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) in EXO RNA samples. The putative lncRNA markers identified in the training set (30 CRC patients and 30 healthy subjects) were verified in the test set (another 30 CRC patients and 30 healthy subjects). We further analyzed the putative lncRNA markers in serum total RNA samples. Results: In the training set, 16 lncRNAs were detectable in serous EXOs, and the expression levels of 7 lncRNAs were significantly different between healthy samples and CRC samples (p<0.05). Stepwise regression analysis showed that the combination of prostate cancer associated 3 (PCA3) and breast cancer anti-estrogen resistance 4 (BCAR4) provided the greatest predictive ability, with an AUC of 0.896 (95% CI: 0.794-0.921, p=0.029). Using the same serum samples, we compared the AUC values of these two lncRNAs in EXO with those in total RNA samples. The AUC values of our serous EXO two-lncRNA signature were markedly higher than those of serum signature (AUC=0.759, 95% CI: 0.696-0.853) for discriminating CRC patients from controls. The predictor was remarkably stable when applied to the test set comprising 30 CRC patients and 30 matched controls, with an AUC of 0.875. The AUC values of the serous EXO two-lncRNA signature for the test set were also markedly higher than those of serum signature (AUC=0.742 95% CI: 0.653-0.801) for discriminating CRC patients from controls. The results indicated that the two-lncRNA signature in serous EXO is an accurate biomarker for CRC diagnosis Conclusions: The PCA3 and BCAR4 signature in serous EXOs may facilitate the detection of CRC and serve as the basis for further studies of the clinical value of circulating lncRNAs in maintaining surveillance and forecasting prognosis. Citation Format: Peng Qi, Lei Dong, Wanrun Lin, Xiaoyan Zhou, Xiang Du. A two-lncRNA signature in serous exosomes serves as a new biomarker for colorectal cancer diagnosis. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B42.