Journal Article

Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers

Hirano, Naohiro, Masamune, Atsushi, Kusaka, Akiko, Nakagawa, Kei, Yasuda, Jun, Soma, Satoshi, Sato, Hideaki, Ito, Shin, Ando, Mika, Kashiwagi, Ryosuke, Inoue, Koetsu, Asano, Naoki, Murakami, Keigo, Aoki, Shuichi, Yoshimachi, Shingo, Iseki, Masahiro, Kume, Kiyoshi, Unno, Michiaki, Zhang, Jie, Mizuma, Masamichi

2024

Overview

Liquid biopsy (LB) is an essential tool for obtaining tumor‐derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell‐free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor‐derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers. A multigene panel for plasma liquid biopsy (LB) can also be applied to bile cell‐free DNA to identify mutations in biliary duct cancers. A machine learning approach was successfully applied to classify possible tumor‐derived variants among the prefiltered variant calls of a multigene panel. Bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Aged / Aged, 80 and over / Analysis / Bile / Bile Duct Neoplasms - genetics / Bile Duct Neoplasms - pathology / Bile ducts / biliary duct cancer / Biliary tract / Biliary tract diseases / Bioinformatics / Biomarkers, Tumor - genetics / Biopsy / Blood levels / Cancer / Cell-Free Nucleic Acids - blood / Cell-Free Nucleic Acids - genetics / Cholangiocarcinoma / Cholangiocarcinoma - genetics / Cholangiocarcinoma - pathology / Circulating Tumor DNA - blood / Circulating Tumor DNA - genetics / Diagnosis / Endoscopy / Female / Females / Gallbladder / Gene mutations / Genes / Genetic aspects / Humans / Insulinoma / liquid biopsy / Liquid Biopsy - methods / Machine Learning / Male / Middle Aged / multigene panel / Mutation / Oncology, Experimental / Original / ORIGINAL ARTICLE / Pancreatic cancer / Pancreatic carcinoma / Patients / Plasma / Point mutation / Tumors