Exosomal MicroRNA signature acts as an efficient biomarker for non-invasive diagnosis of gallbladder carcinoma
Pinghua Yang, Fengliang Song, Xinwei Yang, Xingzhou Yan, Xinyu Huang, Zhengjun Qiu, Zhijian Wen, Liang Chi, X.-T. Xin, Z Q Lei, Kecheng Zhang, Jue Yang, Hu Liu, Hongcheng Wang, Hongcheng Wang, Shijun Xiang, Liang Li, Baohua Zhang, Hongyang Wang, Hongyang Wang
Abstract
Through a three-step study that relies on biomarker discovery, training, and validation, we identified a set of five exosomal microRNAs (miRNAs) that can be used to evaluate the risk of gallbladder carcinoma (GBC), including miR-552-3p, miR-581, miR-4433a-3p, miR-496, and miR-203b-3p. When validated in 102 GBC patients and 112 chronic cholecystitis patients from multiple medical centers, the AUC of this combinatorial biomarker was 0.905, with a sensitivity of 81.37% and a specificity of 86.61%. The performance of this biomarker is superior to that of the standard biomarkers CA199 and CEA and is suited for GBC early diagnosis. The multi-clinicopathological features and prognosis of GBC patients were significantly associated with this biomarker. After building a miRNA-target gene regulation network, cell functions and signaling pathways regulated by these five miRNAs were examined. This biomarker signature can be used in the development of a noninvasive tool for GBC diagnosis, screening and prognosis prediction.