Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma
Abstract The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS...
| Published in: | npj Precision Oncology |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Online Access: | https://doi.org/10.1038/s41698-024-00505-0 |
| _version_ | 1850052541851631616 |
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| author | Abdelrahman Yousef Mahmoud Yousef Saikat Chowdhury Kawther Abdilleh Mark Knafl Paul Edelkamp Kristin Alfaro-Munoz Ray Chacko Jennifer Peterson Brandon G. Smaglo Robert A. Wolff Shubham Pant Michael S. Lee Jason Willis Michael Overman Sudheer Doss Lynn Matrisian Mark W. Hurd Rebecca Snyder Matthew H. G. Katz Huamin Wang Anirban Maitra John Paul Shen Dan Zhao |
| author_facet | Abdelrahman Yousef Mahmoud Yousef Saikat Chowdhury Kawther Abdilleh Mark Knafl Paul Edelkamp Kristin Alfaro-Munoz Ray Chacko Jennifer Peterson Brandon G. Smaglo Robert A. Wolff Shubham Pant Michael S. Lee Jason Willis Michael Overman Sudheer Doss Lynn Matrisian Mark W. Hurd Rebecca Snyder Matthew H. G. Katz Huamin Wang Anirban Maitra John Paul Shen Dan Zhao |
| author_sort | Abdelrahman Yousef |
| collection | DOAJ |
| container_title | npj Precision Oncology |
| description | Abstract The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2–3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3–2.3, p < 0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2–2.4, p = 0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05–2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN’s Know Your Tumor® dataset, n = 408). |
| format | Article |
| id | doaj-art-07e4c9e5f98d41abaef00dd9155ae1ad |
| institution | Directory of Open Access Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| spelling | doaj-art-07e4c9e5f98d41abaef00dd9155ae1ad2025-08-20T00:25:54ZengNature Portfolionpj Precision Oncology2397-768X2024-02-018111310.1038/s41698-024-00505-0Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinomaAbdelrahman Yousef0Mahmoud Yousef1Saikat Chowdhury2Kawther Abdilleh3Mark Knafl4Paul Edelkamp5Kristin Alfaro-Munoz6Ray Chacko7Jennifer Peterson8Brandon G. Smaglo9Robert A. Wolff10Shubham Pant11Michael S. Lee12Jason Willis13Michael Overman14Sudheer Doss15Lynn Matrisian16Mark W. Hurd17Rebecca Snyder18Matthew H. G. Katz19Huamin Wang20Anirban Maitra21John Paul Shen22Dan Zhao23Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterPancreatic Cancer Action Network, Manhattan BeachDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Data Engineering & Analytics, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterPancreatic Cancer Action Network, Manhattan BeachPancreatic Cancer Action Network, Manhattan BeachSheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer CenterDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer CenterSheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterAbstract The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2–3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3–2.3, p < 0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2–2.4, p = 0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05–2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN’s Know Your Tumor® dataset, n = 408).https://doi.org/10.1038/s41698-024-00505-0 |
| spellingShingle | Abdelrahman Yousef Mahmoud Yousef Saikat Chowdhury Kawther Abdilleh Mark Knafl Paul Edelkamp Kristin Alfaro-Munoz Ray Chacko Jennifer Peterson Brandon G. Smaglo Robert A. Wolff Shubham Pant Michael S. Lee Jason Willis Michael Overman Sudheer Doss Lynn Matrisian Mark W. Hurd Rebecca Snyder Matthew H. G. Katz Huamin Wang Anirban Maitra John Paul Shen Dan Zhao Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma |
| title | Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma |
| title_full | Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma |
| title_fullStr | Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma |
| title_short | Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma |
| title_sort | impact of kras mutations and co mutations on clinical outcomes in pancreatic ductal adenocarcinoma |
| url | https://doi.org/10.1038/s41698-024-00505-0 |
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