KRAS G12D Mutation Subtype Is A Prognostic Factor for Advanced Pancreatic Adenocarcinoma
Open accessAbstract
OBJECTIVES: There is no molecular biomarker available in the clinical practice to assess the prognosis of advanced pancreatic carcinoma. This multicenter prospective study aimed to investigate the role of KRAS mutation subtypes within the primary tumor to determine the prognosis of advanced pancreatic cancer. METHODS: The exon-2 KRAS mutation status was tested on endoscopic ultrasound-guided fine-needle aspiration biopsy material (primary tumor; restriction fragment-length polymorphism plus sequencing and TaqMan allelic discrimination) of patients with proven locally advanced and/or metastatic pancreatic ductal carcinoma. We used the Kaplan-Meier method, log-rank test, and Cox's model to evaluate the impact of KRAS status on the overall survival (OS), adjusting for age, stage of disease, clinical performance status, CA 19-9 levels, and treatment. RESULTS: A total of 219 patients (men: 116; mean age: 67±9.4 years) were included: 147 harbored a codon-12 KRAS mutation (G12D: 73; G12V: 53; G12R: 21) and 72 had a wild-type KRAS. There was no difference in the OS between patients with a mutant KRAS (8 months; 95% confidence interval (95% CI): 8.7-12.3) and the wild-type (9 months; 95% CI: 8.7-12.8; hazard ratio (HR): 1.03; P=0.82). However, the patients with a G12D mutation had a significantly shorter OS (6 months; 95% CI: 6.4-9.7) compared with the other patients (OS: 9 months; 95% CI: 10-13; HR: 1.47; P=0.003; i.e., wild type: 9 months, G12V: 9 months, G12R: 14 months). Similar results were observed in the subgroup of 162 patients who received chemotherapy (HR: 1.66; P=0.0013; G12D (n=49): 8 months, wild type (n=56): 10 months, G12V (n=38): 10 months, G12R (n=19): 14 months). Multivariate analyses identified KRAS G12D as an independent predictor for worse prognosis within the entire series (HR: 1.44; P=0.01) and in the subgroup of patients that received chemotherapy (HR: 1.84; P=0.02). CONCLUSIONS: The KRAS G12D mutation subtype is an independent prognostic marker for advanced pancreatic ductal carcinoma. Codon and amino-acid-specific mutations of KRAS should be considered when evaluating the prognoses as well as in trials testing drugs that target RAS and downstream RAS pathways.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
G12D KRAS mutation is significantly associated with worse overall survival in advanced PDAC patients.
“A multicentric study of advanced PDAC patients found that the G12D KRAS mutation was significantly associated with worse overall survival.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [99]
KRAS G12D allele is associated with worse overall survival in advanced PAAD compared to patients with WT KRAS, KRAS G12R, or KRAS G12V.
“the KRAS G12D allele is associated with worse overall survival in advanced PAAD, when compared to patients with WT KRAS, KRAS G12R, or KRAS G12V25”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [25]
In locally advanced and metastatic PDAC, KRAS mutation has been found either negatively associated or not associated with survival with chemotherapy.
“In locally advanced and metastatic PDACs, KRAS mutation was found to be either negatively associated with or not associated with survival with chemotherapy (61, 62).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 40 · Cited by 205
Research works printed but not linked: 1
- Hartley ML, Bade NA, Prins PA et al. Pancreatic cancer, treatment options, and GI-4000. Hum Vaccin Immunother 2015; 11: 931–937. 25933185 PMC4514241
- Authors
- Bournet, B., Muscari, F., Buscail, C., Assenat, E., Barthet, M., Hammel, P., Selves, J., Guimbaud, R., Cordelier, P., & Buscail, L.
- Affiliations
- Inserm (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Hôpital Pontchaillou (FR)
- Aix-Marseille Université (FR)
- Hôpital Beaujon (FR)
- Corresponding author
- Buscail, Camille
- Buscail, Louis
- ORCID
- Venue
- Clinical and Translational Gastroenterology
- Published
- 2016-03
- Volume
- 7
- Issue
- 3
- Pages
- e157
- ISSN
- 2155-384X (ISSN-L)
- PMC
- PMC4822095
- OpenAlex
- W2316733897
- Cited by
- 205
- References
- 40
- Citations by year
- 2026: 9 · 2025: 26 · 2024: 24 · 2023: 18 · 2022: 30 · 2021: 28 · 2020: 25 · 2019: 18 · 2018: 9 · 2017: 15 · 2016: 3
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Clinical and Translational Gastroenterology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- KRAS G12D mutation, pancreatic ductal carcinoma, advanced pancreatic cancer, prognostic factors, overall survival, G12V mutation, KRAS wild-type, metastatic pancreatic cancer, locally advanced pancreatic cancer, endoscopic ultrasound-guided fine-needle aspiration, chemotherapy response, molecular subtyping, CA19-9
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
