An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer
Secretin-stimulated pancreatic juice (PJ), collected from the duodenum, presents a valuable biomarker source for the (earlier) detection of pancreatic cancer (PC). Here, we evaluate the feasibility and performance of shallow sequencing to detect copy number variations (CNVs) in cell-free DNA (cfDNA)...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5097 |
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| author | Iris J. M. Levink Malgorzata I. Srebniak Walter G. De Valk Monique M. van Veghel-Plandsoen Anja Wagner Djuna L. Cahen Gwenny M. Fuhler Marco J. Bruno |
| author_facet | Iris J. M. Levink Malgorzata I. Srebniak Walter G. De Valk Monique M. van Veghel-Plandsoen Anja Wagner Djuna L. Cahen Gwenny M. Fuhler Marco J. Bruno |
| author_sort | Iris J. M. Levink |
| collection | DOAJ |
| description | Secretin-stimulated pancreatic juice (PJ), collected from the duodenum, presents a valuable biomarker source for the (earlier) detection of pancreatic cancer (PC). Here, we evaluate the feasibility and performance of shallow sequencing to detect copy number variations (CNVs) in cell-free DNA (cfDNA) from PJ for PC detection. First, we confirmed the feasibility of shallow sequencing in PJ (n = 4), matched plasma (n = 3) and tissue samples (n = 4, microarray). Subsequently, shallow sequencing was performed on cfDNA from PJ of 26 cases (25 sporadic PC, 1 high-grade dysplasia) and 19 controls with a hereditary or familial increased risk of PC. 40 of the 45 PJ samples met the quality criteria for cfDNA analysis. Nine individuals had an 8q24 gain (oncogene MYC; 23%; eight cases (33%) and one control (6%), <i>p</i> = 0.04); six had both a 2q gain (STAT1) and 5p loss (CDH10; 15%; four cases (7%) and two controls (13%), <i>p</i> = 0.72). The presence of an 8q24 gain differentiated the cases and controls, with a sensitivity of 33% (95% CI 16–55%) and specificity of 94% (95% CI 70–100%). The presence of either an 8q24 or 2q gain with a 5p loss was related to a sensitivity of 50% (95% CI 29–71%) and specificity of 81% (95% CI 54–96%). Shallow sequencing of PJ is feasible. The presence of an 8q24 gain in PJ shows promise as a biomarker for the detection of PC. Further research is required with a larger sample size and consecutively collected samples in high-risk individuals prior to implementation in a surveillance cohort. |
| first_indexed | 2024-03-11T06:26:52Z |
| format | Article |
| id | doaj.art-357257056d53474c97692775cb0fa641 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:52Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-357257056d53474c97692775cb0fa6412023-11-17T11:29:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246509710.3390/ijms24065097An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic CancerIris J. M. Levink0Malgorzata I. Srebniak1Walter G. De Valk2Monique M. van Veghel-Plandsoen3Anja Wagner4Djuna L. Cahen5Gwenny M. Fuhler6Marco J. Bruno7Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC, University Medical Center, 3015 CN Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC, University Medical Center, 3015 CN Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC, University Medical Center, 3015 CN Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC, University Medical Center, 3015 CN Rotterdam, The NetherlandsDepartment of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsSecretin-stimulated pancreatic juice (PJ), collected from the duodenum, presents a valuable biomarker source for the (earlier) detection of pancreatic cancer (PC). Here, we evaluate the feasibility and performance of shallow sequencing to detect copy number variations (CNVs) in cell-free DNA (cfDNA) from PJ for PC detection. First, we confirmed the feasibility of shallow sequencing in PJ (n = 4), matched plasma (n = 3) and tissue samples (n = 4, microarray). Subsequently, shallow sequencing was performed on cfDNA from PJ of 26 cases (25 sporadic PC, 1 high-grade dysplasia) and 19 controls with a hereditary or familial increased risk of PC. 40 of the 45 PJ samples met the quality criteria for cfDNA analysis. Nine individuals had an 8q24 gain (oncogene MYC; 23%; eight cases (33%) and one control (6%), <i>p</i> = 0.04); six had both a 2q gain (STAT1) and 5p loss (CDH10; 15%; four cases (7%) and two controls (13%), <i>p</i> = 0.72). The presence of an 8q24 gain differentiated the cases and controls, with a sensitivity of 33% (95% CI 16–55%) and specificity of 94% (95% CI 70–100%). The presence of either an 8q24 or 2q gain with a 5p loss was related to a sensitivity of 50% (95% CI 29–71%) and specificity of 81% (95% CI 54–96%). Shallow sequencing of PJ is feasible. The presence of an 8q24 gain in PJ shows promise as a biomarker for the detection of PC. Further research is required with a larger sample size and consecutively collected samples in high-risk individuals prior to implementation in a surveillance cohort.https://www.mdpi.com/1422-0067/24/6/5097cfDNAcopy number variantCNVliquid biopsyNIPT |
| spellingShingle | Iris J. M. Levink Malgorzata I. Srebniak Walter G. De Valk Monique M. van Veghel-Plandsoen Anja Wagner Djuna L. Cahen Gwenny M. Fuhler Marco J. Bruno An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer International Journal of Molecular Sciences cfDNA copy number variant CNV liquid biopsy NIPT |
| title | An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer |
| title_full | An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer |
| title_fullStr | An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer |
| title_full_unstemmed | An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer |
| title_short | An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer |
| title_sort | 8q24 gain in pancreatic juice is a candidate biomarker for the detection of pancreatic cancer |
| topic | cfDNA copy number variant CNV liquid biopsy NIPT |
| url | https://www.mdpi.com/1422-0067/24/6/5097 |
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