Bile is a reliable and valuable source to study cfDNA in biliary tract cancers
ObjectiveThe aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract carcinoma (BTC).MethodsA total of 13 patients with BTC were enrolled in this cohort. Tumor tissue, bile, and plasma samples w...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.961939/full |
| _version_ | 1828452510670520320 |
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| author | Zhanghui Li Yelei Liu Junhui Fu Joseph Mugaanyi Junrong Yan Caide Lu Jing Huang |
| author_facet | Zhanghui Li Yelei Liu Junhui Fu Joseph Mugaanyi Junrong Yan Caide Lu Jing Huang |
| author_sort | Zhanghui Li |
| collection | DOAJ |
| description | ObjectiveThe aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract carcinoma (BTC).MethodsA total of 13 patients with BTC were enrolled in this cohort. Tumor tissue, bile, and plasma samples were obtained and analyzed using next-generation sequencing for genomic profiling.ResultsBile and plasma samples were collected from all 13 patients, and 11 patients also had matched tumor tissues available. The cell-free DNA (cfDNA) concentration was significantly higher in the bile supernatant than in plasma (median: 1918 vs. 63.1 ng/ml, p = 0.0017). The bile supernatant and pellet had a significantly higher mean mutation allele frequency (MF) than plasma (median: 3.84% vs. 4.22% vs. 0.16%; p < 0.001). Genomic alterations were predominantly missense. Both bile supernatant and pellet had significantly more genomic alterations than plasma (average: 9.3 vs. 7.2 vs. 2.3 alterations per sample; p < 0.01). Among the top 10 most frequent genomic alterations, 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 that between the plasma and tissue was only 35.00% (7/20). MAF of both bile supernatant and pellet was positively correlated with that in tissue samples (ρ < 0.0001, spearman r = 0.777, and ρ < 0.0001, spearman r = 0.787, respectively), but no significant correlation with tissue was found in the plasma (ρ = 0.966, spearman r = 0.008). Furthermore, additional genomic alterations could be detected in bile supernatant and pellet than in tissue. Potential targets for targeted therapy were identified in bile supernatant and pellet. Regarding copy number variation (CNV) and chromosomal instability (CIN) detection, four additional CNVs from two patients were detected in the bile supernatant that was not detected in tissues (i.e., amplification of TERC, IL7R, RICTOR, and TERT). CIN was significantly higher in tumor tissue than in plasma. The CIN of the bile was also significantly higher than that of plasma. There was no significant difference in CIN between the tissue and the bile supernatant.ConclusionThe consistency of all genomic alterations and tumor tissue-determined genomic alteration in the bile supernatant/pellet was significantly higher than in plasma. Bile supernatants/pellets are better for genetic sequencing and may also have potential clinical value to guide targeted therapy and evaluate prognosis. Bile cfDNA may be a feasible substitute for tumor tissue in the genetic testing of patients with BTC. |
| first_indexed | 2024-12-10T23:53:00Z |
| format | Article |
| id | doaj.art-4e2a149d67d546afafa928fab81376e0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T23:53:00Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-4e2a149d67d546afafa928fab81376e02022-12-22T01:28:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.961939961939Bile is a reliable and valuable source to study cfDNA in biliary tract cancersZhanghui Li0Yelei Liu1Junhui Fu2Joseph Mugaanyi3Junrong Yan4Caide Lu5Jing Huang6Department of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, ChinaDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, ChinaDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, ChinaDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, ChinaMedical Department, Nanjing Geneseeq Technology Inc., Nanjing, ChinaDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, ChinaDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, ChinaObjectiveThe aim of this study is to determine the clinical efficacy of bile-derived liquid biopsy compared with plasma and tumor tissue biopsy in patients with biliary tract carcinoma (BTC).MethodsA total of 13 patients with BTC were enrolled in this cohort. Tumor tissue, bile, and plasma samples were obtained and analyzed using next-generation sequencing for genomic profiling.ResultsBile and plasma samples were collected from all 13 patients, and 11 patients also had matched tumor tissues available. The cell-free DNA (cfDNA) concentration was significantly higher in the bile supernatant than in plasma (median: 1918 vs. 63.1 ng/ml, p = 0.0017). The bile supernatant and pellet had a significantly higher mean mutation allele frequency (MF) than plasma (median: 3.84% vs. 4.22% vs. 0.16%; p < 0.001). Genomic alterations were predominantly missense. Both bile supernatant and pellet had significantly more genomic alterations than plasma (average: 9.3 vs. 7.2 vs. 2.3 alterations per sample; p < 0.01). Among the top 10 most frequent genomic alterations, 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 that between the plasma and tissue was only 35.00% (7/20). MAF of both bile supernatant and pellet was positively correlated with that in tissue samples (ρ < 0.0001, spearman r = 0.777, and ρ < 0.0001, spearman r = 0.787, respectively), but no significant correlation with tissue was found in the plasma (ρ = 0.966, spearman r = 0.008). Furthermore, additional genomic alterations could be detected in bile supernatant and pellet than in tissue. Potential targets for targeted therapy were identified in bile supernatant and pellet. Regarding copy number variation (CNV) and chromosomal instability (CIN) detection, four additional CNVs from two patients were detected in the bile supernatant that was not detected in tissues (i.e., amplification of TERC, IL7R, RICTOR, and TERT). CIN was significantly higher in tumor tissue than in plasma. The CIN of the bile was also significantly higher than that of plasma. There was no significant difference in CIN between the tissue and the bile supernatant.ConclusionThe consistency of all genomic alterations and tumor tissue-determined genomic alteration in the bile supernatant/pellet was significantly higher than in plasma. Bile supernatants/pellets are better for genetic sequencing and may also have potential clinical value to guide targeted therapy and evaluate prognosis. Bile cfDNA may be a feasible substitute for tumor tissue in the genetic testing of patients with BTC.https://www.frontiersin.org/articles/10.3389/fonc.2022.961939/fullbiliary tract carcinomabilenext-generation sequencingchromosomal instabilityliquid biopsy |
| spellingShingle | Zhanghui Li Yelei Liu Junhui Fu Joseph Mugaanyi Junrong Yan Caide Lu Jing Huang Bile is a reliable and valuable source to study cfDNA in biliary tract cancers Frontiers in Oncology biliary tract carcinoma bile next-generation sequencing chromosomal instability liquid biopsy |
| title | Bile is a reliable and valuable source to study cfDNA in biliary tract cancers |
| title_full | Bile is a reliable and valuable source to study cfDNA in biliary tract cancers |
| title_fullStr | Bile is a reliable and valuable source to study cfDNA in biliary tract cancers |
| title_full_unstemmed | Bile is a reliable and valuable source to study cfDNA in biliary tract cancers |
| title_short | Bile is a reliable and valuable source to study cfDNA in biliary tract cancers |
| title_sort | bile is a reliable and valuable source to study cfdna in biliary tract cancers |
| topic | biliary tract carcinoma bile next-generation sequencing chromosomal instability liquid biopsy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.961939/full |
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