Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer
Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13116 |
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| author | Iris J. M. Levink Maurice P. H. M. Jansen Zakia Azmani Wilfred van IJcken Ronald van Marion Maikel P. Peppelenbosch Djuna L. Cahen Gwenny M. Fuhler Marco J. Bruno |
| author_facet | Iris J. M. Levink Maurice P. H. M. Jansen Zakia Azmani Wilfred van IJcken Ronald van Marion Maikel P. Peppelenbosch Djuna L. Cahen Gwenny M. Fuhler Marco J. Bruno |
| author_sort | Iris J. M. Levink |
| collection | DOAJ |
| description | Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available. We performed next-generation sequencing on PJ, plasma, and tissue samples and described the presence (and concordance) of mutations in these biomaterials. This study included 26 patients (25 PC and 1 IPMN with HGD), of which 7 were women (27%), with a median age of 71 years (IQR 12) and a median BMI of 23 kg/m<sup>2</sup> (IQR 4). Ten patients with PC (40%) were (borderline) resectable at baseline. Tissue was available from six patients (resection <i>n</i> = 5, biopsy <i>n</i> = 1). A median volume of 2.9 mL plasma (IQR 1.0 mL) and 0.7 mL PJ (IQR 0.1 mL, <i>p</i> < 0.001) was used for DNA isolation. PJ had a higher median cfDNA concentration (2.6 ng/μL (IQR 4.2)) than plasma (0.29 ng/μL (IQR 0.40)). A total of 41 unique somatic mutations were detected: 24 mutations in plasma (2 <i>KRAS</i>, 15 <i>TP53</i>, 2 <i>SMAD4</i>, 3 <i>CDKN2A</i> 1 <i>CTNNB1</i>, and 1 <i>PIK3CA</i>), 19 in PJ (3 <i>KRAS</i>, 15 <i>TP53</i>, and 1 <i>SMAD4</i>), and 8 in tissue (2 <i>KRAS</i>, 2 <i>CDKN2A</i>, and 4 <i>TP53</i>). The mutation detection rate (and the concordance with tissue) did not differ between plasma and PJ. In conclusion, while the concentration of cfDNA was indeed higher in PJ than in plasma, the mutation detection rate was not different. A few cancer-associated genetic variants were detected in both biomaterials. Further research is needed to increase the detection rate and assess the performance and suitability of plasma and PJ for PC (early) detection. |
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| language | English |
| last_indexed | 2024-03-10T23:22:42Z |
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| spelling | doaj.art-9141d1c9956f48ecbeb167a3869dda972023-11-19T08:12:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171311610.3390/ijms241713116Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic CancerIris J. M. Levink0Maurice P. H. M. Jansen1Zakia Azmani2Wilfred van IJcken3Ronald van Marion4Maikel P. Peppelenbosch5Djuna L. Cahen6Gwenny M. Fuhler7Marco J. Bruno8Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsCenter for Biomics, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsCenter for Biomics, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, 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 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 NetherlandsMolecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available. We performed next-generation sequencing on PJ, plasma, and tissue samples and described the presence (and concordance) of mutations in these biomaterials. This study included 26 patients (25 PC and 1 IPMN with HGD), of which 7 were women (27%), with a median age of 71 years (IQR 12) and a median BMI of 23 kg/m<sup>2</sup> (IQR 4). Ten patients with PC (40%) were (borderline) resectable at baseline. Tissue was available from six patients (resection <i>n</i> = 5, biopsy <i>n</i> = 1). A median volume of 2.9 mL plasma (IQR 1.0 mL) and 0.7 mL PJ (IQR 0.1 mL, <i>p</i> < 0.001) was used for DNA isolation. PJ had a higher median cfDNA concentration (2.6 ng/μL (IQR 4.2)) than plasma (0.29 ng/μL (IQR 0.40)). A total of 41 unique somatic mutations were detected: 24 mutations in plasma (2 <i>KRAS</i>, 15 <i>TP53</i>, 2 <i>SMAD4</i>, 3 <i>CDKN2A</i> 1 <i>CTNNB1</i>, and 1 <i>PIK3CA</i>), 19 in PJ (3 <i>KRAS</i>, 15 <i>TP53</i>, and 1 <i>SMAD4</i>), and 8 in tissue (2 <i>KRAS</i>, 2 <i>CDKN2A</i>, and 4 <i>TP53</i>). The mutation detection rate (and the concordance with tissue) did not differ between plasma and PJ. In conclusion, while the concentration of cfDNA was indeed higher in PJ than in plasma, the mutation detection rate was not different. A few cancer-associated genetic variants were detected in both biomaterials. Further research is needed to increase the detection rate and assess the performance and suitability of plasma and PJ for PC (early) detection.https://www.mdpi.com/1422-0067/24/17/13116pancreatic cancerpancreatic juiceplasmabiomarkersDNAmutation |
| spellingShingle | Iris J. M. Levink Maurice P. H. M. Jansen Zakia Azmani Wilfred van IJcken Ronald van Marion Maikel P. Peppelenbosch Djuna L. Cahen Gwenny M. Fuhler Marco J. Bruno Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer International Journal of Molecular Sciences pancreatic cancer pancreatic juice plasma biomarkers DNA mutation |
| title | Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer |
| title_full | Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer |
| title_fullStr | Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer |
| title_full_unstemmed | Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer |
| title_short | Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer |
| title_sort | mutation analysis of pancreatic juice and plasma for the detection of pancreatic cancer |
| topic | pancreatic cancer pancreatic juice plasma biomarkers DNA mutation |
| url | https://www.mdpi.com/1422-0067/24/17/13116 |
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