Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma
Abstract Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
|
| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01382-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825197565045374976 |
|---|---|
| author | Won-Gun Yun Daeun Kim Youngmin Han Wooil Kwon Seong-Geun Lee Jin-Young Jang Daechan Park |
| author_facet | Won-Gun Yun Daeun Kim Youngmin Han Wooil Kwon Seong-Geun Lee Jin-Young Jang Daechan Park |
| author_sort | Won-Gun Yun |
| collection | DOAJ |
| description | Abstract Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation. In this retrospective cohort study, we analyzed 193 surgically treated patients with PDAC between 2009 and 2016. RNA, whole-exome, and KRAS-targeted sequencing data were used to estimate the dosage of the KRAS G12 mutant. Our prognostic scoring system included the mutation dosage from targeted sequencing ( > 0.195, 1 point), maximal tumor diameter at preoperative imaging ( > 20 mm, 1 point), and carbohydrate antigen 19-9 levels ( > 150 U/mL, 1 point). The KRAS mutation dosage exhibited comparable performance with clinical variables for survival prediction. High KRAS mutation dosages activated the cell cycle, leading to high mutation rates and poor prognosis. According to prognostic scoring systems that integrate mutation dosage with clinical factors, patients with 0 points had superior median overall survival of 97.0 months and 1-year, 3-year, and 5-year overall survival rates of 95.8%, 70.8%, and 66.4%, respectively. In contrast, patients with 3 points had worse median overall survival of only 16.0 months and 1-year, 3-year, and 5-year overall survival rates of 65.2%, 8.7%, and 8.7%, respectively. The incorporation of the KRAS G12 mutation dosage variable into prognostic scoring systems can improve clinical variable-based survival prediction, highlighting the feasibility of an integrated scoring system with clinical significance. |
| format | Article |
| id | doaj-art-13e1e7512d2a4182b29d1c259f17c831 |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-13e1e7512d2a4182b29d1c259f17c8312025-02-09T12:14:20ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-01-0157119320310.1038/s12276-024-01382-0Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinomaWon-Gun Yun0Daeun Kim1Youngmin Han2Wooil Kwon3Seong-Geun Lee4Jin-Young Jang5Daechan Park6Department of Surgery and Cancer Research Institute, Seoul National University College of MedicineDepartment of Molecular Science and Technology, Ajou UniversityDepartment of Surgery and Cancer Research Institute, Seoul National University College of MedicineDepartment of Surgery and Cancer Research Institute, Seoul National University College of MedicineDepartment of Molecular Science and Technology, Ajou UniversityDepartment of Surgery and Cancer Research Institute, Seoul National University College of MedicineDepartment of Molecular Science and Technology, Ajou UniversityAbstract Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation. In this retrospective cohort study, we analyzed 193 surgically treated patients with PDAC between 2009 and 2016. RNA, whole-exome, and KRAS-targeted sequencing data were used to estimate the dosage of the KRAS G12 mutant. Our prognostic scoring system included the mutation dosage from targeted sequencing ( > 0.195, 1 point), maximal tumor diameter at preoperative imaging ( > 20 mm, 1 point), and carbohydrate antigen 19-9 levels ( > 150 U/mL, 1 point). The KRAS mutation dosage exhibited comparable performance with clinical variables for survival prediction. High KRAS mutation dosages activated the cell cycle, leading to high mutation rates and poor prognosis. According to prognostic scoring systems that integrate mutation dosage with clinical factors, patients with 0 points had superior median overall survival of 97.0 months and 1-year, 3-year, and 5-year overall survival rates of 95.8%, 70.8%, and 66.4%, respectively. In contrast, patients with 3 points had worse median overall survival of only 16.0 months and 1-year, 3-year, and 5-year overall survival rates of 65.2%, 8.7%, and 8.7%, respectively. The incorporation of the KRAS G12 mutation dosage variable into prognostic scoring systems can improve clinical variable-based survival prediction, highlighting the feasibility of an integrated scoring system with clinical significance.https://doi.org/10.1038/s12276-024-01382-0 |
| spellingShingle | Won-Gun Yun Daeun Kim Youngmin Han Wooil Kwon Seong-Geun Lee Jin-Young Jang Daechan Park Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma Experimental and Molecular Medicine |
| title | Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma |
| title_full | Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma |
| title_fullStr | Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma |
| title_short | Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma |
| title_sort | multiomic quantification of the kras mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma |
| url | https://doi.org/10.1038/s12276-024-01382-0 |
| work_keys_str_mv | AT wongunyun multiomicquantificationofthekrasmutationdosageimprovesthepreoperativepredictionofsurvivalandrecurrenceinpatientswithpancreaticductaladenocarcinoma AT daeunkim multiomicquantificationofthekrasmutationdosageimprovesthepreoperativepredictionofsurvivalandrecurrenceinpatientswithpancreaticductaladenocarcinoma AT youngminhan multiomicquantificationofthekrasmutationdosageimprovesthepreoperativepredictionofsurvivalandrecurrenceinpatientswithpancreaticductaladenocarcinoma AT wooilkwon multiomicquantificationofthekrasmutationdosageimprovesthepreoperativepredictionofsurvivalandrecurrenceinpatientswithpancreaticductaladenocarcinoma AT seonggeunlee multiomicquantificationofthekrasmutationdosageimprovesthepreoperativepredictionofsurvivalandrecurrenceinpatientswithpancreaticductaladenocarcinoma AT jinyoungjang multiomicquantificationofthekrasmutationdosageimprovesthepreoperativepredictionofsurvivalandrecurrenceinpatientswithpancreaticductaladenocarcinoma AT daechanpark multiomicquantificationofthekrasmutationdosageimprovesthepreoperativepredictionofsurvivalandrecurrenceinpatientswithpancreaticductaladenocarcinoma |