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,
Chi Liang,
Xianglei Xin,
Zhengqin Lei,
Kecheng Zhang,
Jue Yang,
Hu Liu,
Hongcheng Wang,
Shijun Xiang,
Liang Li,
Baohua Zhang,
Hongyang Wang
Affiliations
Pinghua Yang
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China
Fengliang Song
School of Medicine, Nantong University, Nantong, Jiangsu Province, China; International Co-operation Laboratory on Signal Transduction, Eastern Hepato-biliary Surgery Institute, Second Military Medical University, Shanghai, China
Xinwei Yang
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China
Xingzhou Yan
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China
Xinyu Huang
Department of General Surgery, Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Zhengjun Qiu
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhijian Wen
Department of General Surgery, No 73 Hospital, China
Chi Liang
The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, China
Xianglei Xin
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China
Zhengqin Lei
Zhongda Hospital of Southeast University, Nanjing, Jiangsu Province, China
Kecheng Zhang
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China
Jue Yang
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China
Hu Liu
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China
Hongcheng Wang
Department of General Surgery, Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Shijun Xiang
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Liang Li
International Co-operation Laboratory on Signal Transduction, Eastern Hepato-biliary Surgery Institute, Second Military Medical University, Shanghai, China; National Center for Liver Cancer, Shanghai, China; Corresponding author
Baohua Zhang
Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China; Corresponding author
Hongyang Wang
International Co-operation Laboratory on Signal Transduction, Eastern Hepato-biliary Surgery Institute, Second Military Medical University, Shanghai, China; National Center for Liver Cancer, Shanghai, China; National Laboratory for Oncogenes and Related Genes, Cancer Institute, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China; Corresponding author
Summary: 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.
