Cell-Free DNA in Plasma Reveals Genomic Similarity Between Biliary Tract Inflammatory Lesion and Biliary Tract Cancer

Similar clinical manifestations and imaging features between biliary tract inflammatory lesion (BTI) and biliary tract cancer (BTC) pose significant challenges for the management of BTC. To date, the molecular characteristics of the relationship between biliary tract inflammatory lesion and biliary tract cancer remain poorly elucidated. Here, we performed target deep sequencing on 45 BTC patients and 31 BTI patients based on cell-free DNA (cfDNA) in plasma. We characterized the mutational features of 93 cancer-related genes for BTI and BTC. A total of 41% of genes showed concordance between BTI and BTC patients. Mutation burden in cfDNA exhibits a correlation with the levels of cancer antigen 19-9 (CA19-9) (r = 0.420) and carcinoembryonic antigen (CEA) (r = 0.580). Tumor protein p53 (TP53) and low-density lipoprotein receptor-related protein 1B (LRP1B) exhibit the most significant disparity in mutation frequencies between BTC and BTI. Additionally, based on cfDNA, we developed an algorithm, allele fraction variance (AFV), as a supplemental tool for BTC prognosis. Preoperative AFV performed better in predicting prognosis than postoperative one. These findings indicate that genetic mutations in cfDNA accumulate during the progression from BTI to BTC. cfDNA in plasma implies a prognostic value for the BTC.

The online version contains supplementary material available at 10.1007/s43657-024-00160-2.