Molecular diagnosis of pancreatobiliary tract cancer by detecting mutations and methylation changes in bile samples

作者：Shun He, Fanxin Zeng, Huihui Yin, Pei Wang, Yinlei Bai, Qianqian Song, Jiangtao Chu, Zhen Huang, Yumeng Liu, Hong Liu, Qichen Chen, Li Liu, Jun Zhou, Hanjie Hu, Xingchen Li, Tengyan Li, Guiqi Wang, Jianqiang Cai, Yuchen Jiao, Hong Zhao · 发表于：EClinicalMedicine · 年份：2022 · DOI：10.1016/j.eclinm.2022.101736 · 被引用次数：16 · 研究领域：Gallbladder and Bile Duct Disorders、Cholangiocarcinoma and Gallbladder Cancer Studies、Pediatric Hepatobiliary Diseases and Treatments

Background: Patients with pancreatobiliary tract cancer usually have a poor clinical outcome, with a 5-year overall survival rate below 20%. This is mainly associated with the late diagnosis. In addition, the standard-of-care for patients with malignant biliary stenosis involves a major surgery, the Whipple procedure. An accurate preoperative diagnosis, including differentiation from benign diseases, is critical to avoid unnecessary treatment. Here we developed BileScreen, a sensitive detection modality for the diagnosis of pancreatobiliary tract cancer based on massively parallel sequencing mutation and methylation changes in bile samples. Methods: A total of 338 patients, from five hospitals in China, with pancreatobiliary system disorders were enrolled in this study between November 2018 and October 2020, and 259 were included for the analysis of BileScreen. We profiled 23 gene mutations and 44 genes with methylation modifications in parallel from bile samples, and set up a model for the detection of malignancy based on multi-level biomarkers. Findings: We applied the BileScreen assay in a training cohort (n = 104) to set up the model and algorithm. The model was further evaluated in a validation cohort (n = 105), resulting in 92% sensitivity and 98% specificity. The performance of BileScreen was further assessed in a prospective test cohort (n = 50) of patients diagnosed with suspicious or negative pathology by endoscopic retrograde cholangiopancreatography and were confi...