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. 2025 Jul 1;25(1):1080.
doi: 10.1186/s12885-025-14461-w.

Elevated KRAS protein level is associated with better survival in pancreatic cancer

S M Stålberg  1   2   3 , L Silwal-Pandit  4 , J Hamfjord  4   5 , D J H Nebdal  4 , J Lehtiö  6 , O C Lingjærde  4   7 , B S Skålhegg  8 , E H Kure  4   9
Affiliations

Elevated KRAS protein level is associated with better survival in pancreatic cancer

S M Stålberg et al. BMC Cancer. .

Abstract

Background: Activating somatic KRAS mutations in hotspot loci occur almost universally (> 95%) in pancreatic ductal adenocarcinoma (PDAC). Both the presence of a KRAS mutation and high mRNA expression levels of KRAS in tumor tissue have been associated with worse outcome. Less is known about the expression of KRAS at the protein level and its association with clinical and molecular parameters. In the present study, we investigated the prognostic significance of the KRAS protein level and its relation to KRAS mutation status and the mRNA expression level.

Methods: A total of 41 PDAC tumors were screened for seven KRAS mutations (p.G12D, p.G12V, p.G12R, p.G12C, p.G12S, p.G13D, p.G12A) by the Wobble-enhanced ARMS method. Whole transcriptome and proteome profiles were obtained using mRNA microarrays (Agilent) and quantitative mass spectrometry-based proteomics (HiRIEF LC-MS/MS), respectively. The clinical outcome was overall survival (OS).

Results: KRAS mutations were identified in 88% of the tumors with p.G12D and p.G12V mutations being the most frequent. Tumors with p.G12V mutation had significantly higher KRAS mRNA expression than tumors with p.G12D, p.G12C, p.G12R or no mutation identified (P < 0.01). KRAS protein levels did not associate significantly to neither KRAS mRNA levels (Spearman's rho = 0.18, P = 0.28) nor type of KRAS mutation. High KRAS protein level and mutation p.G12V were found to be significantly associated with better (P < 0.01) and worse OS (P < 0.05), respectively.

Conclusions: The KRAS protein level correlated poorly with KRAS mRNA expression level and was not significantly associated with the type of mutation present. Interestingly, we found that patients with high KRAS protein level in their tumors had a better clinical outcome.

Keywords: KRAS mRNA expression; KRAS mutation; KRAS protein level; PDAC; Pancreatic cancer.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The patients were included in the specific biobank at Oslo University Hospital entitled “Thematic Research Area Pancreatic Cancer”. This study, linked to the specific biobank, was approved by the Regional Committee for Medical and Health Research Ethics with reference REK 2015/738. The patient’s informed signed consent covers collection and analyses of biological material in addition to clinical information. The research was conducted in accordance with the WMA Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The flowchart illustrates the patients, tissue samples, and methods included in the present study. * Two adjacent benign tissue samples each from five patients with PDAC were included in the proteomics analysis. ** Two pancreatic tissue samples each from five patients with benign pancreatic disease were included in the proteomics analysis
Fig. 2
Fig. 2
KRAS expression levels in PDAC and benign pancreatic tissues. A: KRAS mRNA expression in malignant (N = 38) and benign pancreatic tissues (N = 12), B: KRAS protein levels in malignant (N = 41) and benign (N = 20) pancreatic tissues. Wilcoxon’s Rank Sum Test was used to calculate p-values
Fig. 3
Fig. 3
Kaplan Meier curves of overall survival of the PDAC patients based on A: KRAS mRNA expression above and below median, and B: KRAS protein levels above and below median. Three patients without overlapping protein and mRNA data, one patient with metastasis at diagnosis, and one patient with non-standard treatment were excluded from the analyses. The associations between the omics-levels and OS were tested using the log-rank test
Fig. 4
Fig. 4
Boxplots illustrating association of KRAS expression with type of KRAS mutation in PDAC patients at A: mRNA level (N = 38), and B: protein level (N = 41). The Kruskal–Wallis Rank Sum Test was used to calculate p-values
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