Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China

Abstract Purpose The Kirsten rat sarcoma viral oncogene (KRAS) is the most frequently mutated oncogene in human cancers. Significant advancements have been made in targeted therapy and immunotherapy for this gene in recent years, underscoring the importance of comprehensively understanding the genom...

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Main Authors: Liyuan Wu, Wei Rao, Lei Guo, Fanshuang Zhang, Weihua Li, Jianming Ying
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Journal of Cancer Research and Clinical Oncology
Subjects:
Online Access:https://doi.org/10.1007/s00432-025-06118-9
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author Liyuan Wu
Wei Rao
Lei Guo
Fanshuang Zhang
Weihua Li
Jianming Ying
author_facet Liyuan Wu
Wei Rao
Lei Guo
Fanshuang Zhang
Weihua Li
Jianming Ying
author_sort Liyuan Wu
collection DOAJ
description Abstract Purpose The Kirsten rat sarcoma viral oncogene (KRAS) is the most frequently mutated oncogene in human cancers. Significant advancements have been made in targeted therapy and immunotherapy for this gene in recent years, underscoring the importance of comprehensively understanding the genomic landscape of KRAS across various cancer types. Methods Using next-generation sequencing (NGS) technology and a panel of 520 genes, KRAS mutations, tumor mutation burden (TMB), and microsatellite instability (MSI-H) status were investigated. Results An analysis of 10,820 tumor samples found KRAS mutations in 19.97% of cases. Pancreatic cancer showed the highest prevalence of KRAS mutations at 73.51%, while colorectal at 41.45%, uterine at 21.23%, and lung cancer at 11.24%. KRAS G12D mutation is most common in pancreatic, colorectal, and gastric cancers, while KRAS G12V mutation is predominant in uterine cancer, and KRAS G12C mutation is most frequent in lung cancer. Significant correlations were found between TMB and KRAS G13D/G12V mutations in colorectal cancer. KRAS G13D notably affected TMB in uterus cancer, while KRAS G12C mutation was linked to high TMB in lung cancer. Moreover, statistical analysis revealed a significant association between KRAS G13D/G12V mutations and MSI-H in colorectal cancer. Conclusions KRAS mutations were most frequent in cancers of the digestive, female reproductive, and respiratory systems. Specific KRAS mutations are associated with TMB and MSI in various cancer types.
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spelling doaj-art-2ae75c406c974d1da898d6b3a97f09ee2025-08-20T03:01:41ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-02-0115121910.1007/s00432-025-06118-9Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in ChinaLiyuan Wu0Wei Rao1Lei Guo2Fanshuang Zhang3Weihua Li4Jianming Ying5Departments of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartments of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartments of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartments of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartments of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartments of Pathology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Purpose The Kirsten rat sarcoma viral oncogene (KRAS) is the most frequently mutated oncogene in human cancers. Significant advancements have been made in targeted therapy and immunotherapy for this gene in recent years, underscoring the importance of comprehensively understanding the genomic landscape of KRAS across various cancer types. Methods Using next-generation sequencing (NGS) technology and a panel of 520 genes, KRAS mutations, tumor mutation burden (TMB), and microsatellite instability (MSI-H) status were investigated. Results An analysis of 10,820 tumor samples found KRAS mutations in 19.97% of cases. Pancreatic cancer showed the highest prevalence of KRAS mutations at 73.51%, while colorectal at 41.45%, uterine at 21.23%, and lung cancer at 11.24%. KRAS G12D mutation is most common in pancreatic, colorectal, and gastric cancers, while KRAS G12V mutation is predominant in uterine cancer, and KRAS G12C mutation is most frequent in lung cancer. Significant correlations were found between TMB and KRAS G13D/G12V mutations in colorectal cancer. KRAS G13D notably affected TMB in uterus cancer, while KRAS G12C mutation was linked to high TMB in lung cancer. Moreover, statistical analysis revealed a significant association between KRAS G13D/G12V mutations and MSI-H in colorectal cancer. Conclusions KRAS mutations were most frequent in cancers of the digestive, female reproductive, and respiratory systems. Specific KRAS mutations are associated with TMB and MSI in various cancer types.https://doi.org/10.1007/s00432-025-06118-9Malignant tumorsNext-generation sequencingKRAS mutationTumor mutation burdenMicrosatellite instability
spellingShingle Liyuan Wu
Wei Rao
Lei Guo
Fanshuang Zhang
Weihua Li
Jianming Ying
Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China
Journal of Cancer Research and Clinical Oncology
Malignant tumors
Next-generation sequencing
KRAS mutation
Tumor mutation burden
Microsatellite instability
title Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China
title_full Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China
title_fullStr Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China
title_full_unstemmed Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China
title_short Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China
title_sort pan cancer analysis to character the clinicopathological and genomic features of kras mutated patients in china
topic Malignant tumors
Next-generation sequencing
KRAS mutation
Tumor mutation burden
Microsatellite instability
url https://doi.org/10.1007/s00432-025-06118-9
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