AUTHOR=Li Zhanghui , Liu Yelei , Fu Junhui , Mugaanyi Joseph , Yan Junrong , Lu Caide , Huang Jing 

TITLE=Bile is a reliable and valuable source to study cfDNA in biliary tract cancers

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.961939

DOI=10.3389/fonc.2022.961939

ISSN=2234-943X

ABSTRACT=Objective: To determine the clinical efficacy of bile duct biopsy compared to plasma and tumor tissue biopsy in patients with biliary tract carcinoma. Methods: Data of 13 patients with biliary tract carcinoma was evaluated, matched bile, plasma and tumor tissue samples were obtained from 11 patients. Bile and plasma samples were obtained from another 2. All samples were examined using next-generation sequencing. Results: Bile and plasma samples were collected in all 13 patients. 2 patients did not have tissue samples. cfDNA concentration was significantly higher in bile supernatant than in plasma (median: 1918 ng/ml vs 63.1 ng/ml, P = 0.0017). The bile supernatant and pellet had a significantly higher mean mutation abundance (median: 3.84% vs 4.22% vs 0.16%, P < 0.001). Mutations were predominantly missense. Both the supernatant and pellet had significantly more mutations than plasma. Among the 10 high-frequency mutations, the consistency between bile supernatant and tumor tissue was 90.00% (18/20), that between bile pellet and tumor tissue was 85.00% (17/20), and the consistency between plasma and tissue was only 35.00% (7/20). Bile supernatant/pellet was positively correlated with Mutant Allele Frequency (MAF) in tissue samples, p<0.0001; but no significant correlation with tissue was found in the plasma (p= 0.48, r=0.14). Furthermore, bile supernatant and pellet can be used to detect tumor tissue specific mutations. Potential targeted therapy sites were identified in the supernatant and pellet. This may be beneficial to patient treatment. In regards to copy number and Chromosomal Instability (CIN) detection, copy number variation was detected in the supernatant of 2 patients that could not be detected in 4 tumor tissue. The CIN was significantly higher in the tumor tissue than in plasma. CIN of the bile was also significantly higher than that of plasma. There was no significant difference in the supernatant. Conclusion: The consistency of mutations and tumor tissue specific mutations in the bile supernatant/pellet is significantly higher than that in plasma. Bile supernatant/pellet are better for next-generation sequencing and may also have potential clinical value for guiding targeted therapy and prognosis. Bile cfDNA detection may be a feasible replacement for tumor tissue for genetic testing.