Liquid biopsy of bile for the molecular diagnosis of gallbladder cancer

ABSTRACT

Introduction: Tissue sampling of gallbladder cancer (GBCa) is challenging because of the anatomy of the gallbladder. The aim of this study is to investigate the possibility of diagnosing GBCa patients by performing a liquid biopsy of bile in addition to current diagnostic methods.

Methods: Thirty patients with GBCa were enrolled in this study. Cytological examination was performed in all patients. Using next generation sequencing (NGS), DNA isolated from the bile and tumor tissue was analyzed for mutations in 49 oncogenes. We also compared these mutations with cytology results.

Results: 57.1% of DNA samples from tumor tissue were positive for a mutation. In these patients, 87.5% of the bile circulating tumor DNA (ctDNA) samples had the same mutation. The concordance rate between bile ctDNA and tissue DNA samples was 85.7%, and the mutation frequencies detected in ctDNA were approximately half of what was detected in tumor tissue DNA. On the other hand, the sensitivity of the cytological and bile ctDNA analyses was 45.8% and 58.3%, respectively. The concordance rate between cytology and bile ctDNA analyses was 87.5%.

Conclusions: Mutated tumor DNA could be detected in bile by NGS. Liquid biopsy of bile might help us to diagnose GBCa because of higher sensitivity and positive predict value compared to cytology with ERCP.

KEYWORDS:

• CtDNA
• bile
• circulating tumor DNA
• gallbladder cancer
• liquid biopsy

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by KAKENHI (16K19345) and by a grant from the Japanese Society of Gastroenterology.

Authors' contributions

Dr. HK designed the study and drafted the manuscript. Dr. KN was responsible for the revision of the manuscript. Drs. KM and HK were responsible for the diagnosis and treatment of patients. Drs. SA, CD and HM assisted Dr. HK in analyzing the data. Dr. HO supervised the manuscript preparation. All authors approved the final manuscript.

Additional information

Funding

This work was partially supported by KAKENHI (16K19345) and by a grant from the Japanese Society of Gastroenterology.