KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer.
cohort study
oncogene
pancreatectomy
pancreatic neoplasm
sequence analysis
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
revised:
13
04
2022
received:
14
01
2022
accepted:
30
04
2022
pubmed:
15
5
2022
medline:
14
9
2022
entrez:
14
5
2022
Statut:
ppublish
Résumé
KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi-institutional cohort of 1162 pancreatic cancer patients with formalin-fixed paraffin-embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS-mutant to KRAS-wild-type tumors, 1.04 [95% CI, 0.62-1.75] and 1.05 [95% CI, 0.60-1.84], respectively). Among KRAS-mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13-1.42; p
Identifiants
pubmed: 35567350
doi: 10.1111/cas.15398
pmc: PMC9459293
doi:
Substances chimiques
Biomarkers, Tumor
0
KRAS protein, human
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3097-3109Subventions
Organisme : Daiwa Securities Health Foundation
Organisme : Japan Agency for Medical Research and Development
ID : JP21ck0106557
Organisme : Japan Society for the Promotion of Science
ID : JP19K08362
Organisme : Japan Society for the Promotion of Science
ID : JP20K07414
Organisme : Japan Society for the Promotion of Science
ID : JP21K15368
Organisme : Japan Society for the Promotion of Science
ID : JP21K15393
Organisme : Takeda Science Foundation
Informations de copyright
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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