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

doi:10.1016/j.isci.2022.104816

Exosomal MicroRNA signature acts as an efficient biomarker for non-invasive diagnosis of gallbladder carcinoma

iScience. 2022 Jul 21;25(9):104816. doi: 10.1016/j.isci.2022.104816. eCollection 2022 Sep 16.

Authors

Pinghua Yang¹, Fengliang Song^{2

3}, Xinwei Yang¹, Xingzhou Yan¹, Xinyu Huang⁴, Zhengjun Qiu⁵, Zhijian Wen⁶, Chi Liang⁷, Xianglei Xin¹, Zhengqin Lei⁸, Kecheng Zhang¹, Jue Yang¹, Hu Liu¹, Hongcheng Wang⁴, Shijun Xiang⁵, Liang Li^{3

9}, Baohua Zhang¹, Hongyang Wang^{3

9

10}

Affiliations

¹ Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China.
² School of Medicine, Nantong University, Nantong, Jiangsu Province, China.
³ International Co-operation Laboratory on Signal Transduction, Eastern Hepato-biliary Surgery Institute, Second Military Medical University, Shanghai, China.
⁴ Department of General Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Department of General Surgery, No 73 Hospital, China.
⁷ The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, China.
⁸ Zhongda Hospital of Southeast University, Nanjing, Jiangsu Province, China.
⁹ National Center for Liver Cancer, Shanghai, China.
¹⁰ National Laboratory for Oncogenes and Related Genes, Cancer Institute, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

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.

Keywords: Cancer; Cancer systems biology; Health sciences.