What this research found
Not every KRAS mutation in pancreatic cancer carries the same prognosis. Using sequencing and clinical data for 2,336 pancreatic ductal adenocarcinoma (PDAC) patients from the MSK 2024 cohort on cBioPortal, this analysis mapped which KRAS variants occur and how long the patients carrying each one survived. Median overall survival ranged from 15.52 months for G12D to 20.45 months for G12R — a gap of roughly five months that was significant by log-rank test (p = 0.0013).
- KRAS is mutated in 93.9% of the 2,336-patient cohort, and three variants dominate: among KRAS-mutant tumours, G12D accounts for 40.66% (892 cases), G12V for 32.18% (706), and G12R for 16.04% (352).
- Survival differed significantly across those three variants in the 1,892 patients analysed (log-rank p = 0.0013). Median overall survival was 20.45 months for G12R, 17.95 months for G12V, and 15.52 months for G12D.
- The most common variant carries the shortest survival. G12D is both the single most frequent mutation and the worst-prognosis one, so the roughly five-month deficit against G12R falls on the largest patient group.
- Mutations at codon 61 are uncommon — Q61H in 5.06% of KRAS-mutant cases (111 patients) and Q61R in 1.69% (37) — and the survival comparison was restricted to the three commonest variants.
- The survival ordering is interpreted through published variant biology, including impaired PI3K signalling for G12R and an immunosuppressive tumour environment for G12D, but those mechanisms come from prior literature rather than from experiments run here.
How it was done
Mutation and clinical tables for the MSK 2024 PDAC cohort were retrieved from cBioPortal, where all 2,336 samples had been profiled by MSK-IMPACT targeted sequencing covering 505 genes at over 500x coverage. KRAS variants were tabulated by amino-acid change, then Kaplan-Meier curves with a log-rank test compared overall survival across the three commonest variants in 1,892 patients, over a median follow-up of 13.54 months. Death was recorded for 630 of 870 G12D patients, 447 of 681 with G12V, and 200 of 341 with G12R. The output was a 17-page manuscript with six figures and 23 verified citations.
Data sources
- cBioPortal — Pancreatic Adenocarcinoma (MSK, Nature Medicine 2024), 2,336 patients
- MSK-IMPACT targeted sequencing panel — 505 genes at over 500x coverage
- Singhi et al., JAMA Network Open (2024) and Collisson et al., Journal of Clinical Investigation (2024)
- Bailey et al., Nature (2016) and TCGA, Cancer Cell (2017)
Limitations
The survival comparison is univariate: no Cox proportional-hazards model was fitted, and limited clinical covariate data meant no adjustment for stage, treatment, or performance status. Differential use of FOLFIRINOX versus gemcitabine-based regimens could therefore contribute to the variant differences observed.
Figures from this analysis
How this research was produced
K-Dense Web planned and ran this cancer biology investigation end to end — gathering the sources, carrying out the analysis, producing the figures, and drafting the report. The full session transcript, including every intermediate step, is available to view.
