ArticleAnnals of surgical oncology2022
Comprehensive Analysis of Somatic Mutations in Driver Genes of Resected Pancreatic Ductal Adenocarcinoma Reveals KRAS G12D and Mutant TP53 Combination as an Independent Predictor of Clinical Outcome.
Article in Annals of surgical oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Benefits and challenges of adding BKM120 to a BI-3406 plus trametinib combination therapy.BMC cancer · 2026Article
- Prognostic Implications of Codon-SpecificJCO precision oncology · 2026Article
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- Advances in biomarkers of resistance to KRAS mutation-targeted inhibitors.Discover oncology · 2025Review
- Functional Analysis of Rare RAS Variants of Unknown Significance.Cancer research communications · 2025Article
- Distinct clinical outcomes and biological features of specific KRAS mutants in human pancreatic cancer.Cancer cell · 2024Article
- KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways.Cells · 2024Review
- Sex Matters-Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer.Cancers · 2024Article
- The Clinical Implications of KRAS Mutations and Variant Allele Frequencies in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2024Review
- Next-generation sequencing of pancreatic cyst wall specimens obtained using micro-forceps for improving diagnostic accuracy.Endoscopy international open · 2023Article
- Pathogenic genomic alterations in Chinese pancreatic cancer patients and their therapeutical implications.Cancer medicine · 2023Article
- Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2023Article
- KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration.Journal of clinical medicine · 2023Review
- Prognostic utility of TME-associated genes in pancreatic cancer.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrognosis in pancreatic ductal adenocarcinoma (PDAC) remains poor despite improved systemic therapies and surgical techniques. The identification of biomarkers to advance insight in tumor biology and achieve better individualized prognostication could help improve outcomes. Our aim was to elucidate the prognostic role of the four main driver mutations (KRAS, TP53, SMAD4, CDKN2A) and their combinations in resected PDAC. PATIENTS AND
methodsA retrospective analysis was conducted utilizing the cBioPortal database and National Cancer Institute's Cancer Genomic Atlas (TCGA) on patients in whom next-generation sequencing was performed on upfront resected PDAC from 2012 to 2020. Multivariable Cox regression was implemented to elucidate risk-adjusted predictors of overall (OS) and recurrence-free survival (RFS). Results were validated employing a Johns Hopkins Hospital (JHH) cohort.'
resultsIn the discovery cohort (n = 587), increased number of mutated driver genes was associated with worse OS (p = 0.047). Specifically, patients with mutations in ≥ 2 driver genes had worse OS than ≤ 1 mutated gene (18.2 versus 32.3 months, p = 0.033). Co-occurrence of mutant (mt)KRAS p.G12D with mtTP53 (median OS, 25.9 months) conferred better prognosis than co-occurrence of other mtKRAS variants (p.G12V/R/other) with mtTP53 (median OS, 16.9 months, p = 0.038). The findings were validated using a JHH cohort. Multivariable risk-adjustment found co-occurrence of mtKRAS p.G12D with mtTP53 to be an independent predictor of beneficial OS and RFS [HR (95% CI): 0.18 (0.03-0.81) and 0.31 (0.11-0.89) respectively].
conclusionIn chemo-naïve resected PDAC, combinations of mutations in the four driver genes are associated with prognosis. In patients with combined mtKRAS and mtTP53, KRAS p.G12D variant confers a better OS and RFS.
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