Pathology & Oncology Research

, Volume 25, Issue 1, pp 269–278 | Cite as

Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients

  • Javier Martinez-UserosEmail author
  • Weiyao Li
  • Tihomir Georgiev-Hristov
  • Maria J. Fernandez-Aceñero
  • Aurea Borrero-Palacios
  • Nuria Perez
  • Angel Celdran
  • Jesus Garcia-FoncillasEmail author
Original Article


Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and its incidence is rising worldwide. Although survival can be improved by surgical resection, when detected at an early stage, this type of cancer is usually asymptomatic, and disease becomes only apparent after metastasis. Adjuvant treatment does not improve survival, thus after surgery there is a lack of predictive and prognosis biomarkers to predict treatment response and survival. The mitogen-activated protein-kinase and phosphoinositide 3-kinase signalling pathways play a crucial role in cancer development and progression. Especially, activated RAS proteins promote cell proliferation through constitutive stimulation of the downstream effectors RAF-MEK-ERK and PI3K-AKT. Mutational status of NRAS is required in several types of cancer like colorectal or cutaneous melanoma. However, mutations in this gene are very scarce in PDAC patients, and NRAS determination is not usually performed in clinical practice for this kind of tumor. In this study, we analyse the association between NRAS protein expression and progression-free survival and overall survival of an homogenous cohort of pancreatic ductal adenocarcinoma patients from a single-centre. Interestingly, we found that patients with high expression not only showed longer progression-free survival than those patients with low expression (22 versus 9 months, respectively) (P = 0.013), but also longer overall survival (43 versus 19 months, respectively) (P = 0.020). These results confirm NRAS expression could be used to differentiate patients according to their prognosis. Proportional hazard model revealed NRAS expression together with grade of differentiation as pathological variables to predict patient’s outcome.


Pancreatic ductal adenocarcinoma PDAC NRAS KRAS TGCA Biomarker Progression-free survival Overall survival Grade of differentiation 



We thank Oliver Shaw, PhD (FIIS-FJD) for editing the manuscript for English usage, clarity, and style. We also A. Cazorla MD, PhD for a double-blind tissue immunostainings evaluation and quantification.

Author’s Contribution

J.M.-U. designed the study, analyse data, draft the article and is the guarantor for the article; W.L. and A.B.P. performed experiments; T.G.-H. and M.J.F.-A. performed patients database; N.P., A.C. and J.G.-F. revised critically the manuscript.


This work has been carried out with Spanish Health Research Project Funds PI16/01468 from “Instituto de Salud Carlos III FEDER” (J.G.-F.), of the Spanish Ministry of Economy, Industry and Competitiveness.

Compliance with Ethical Standards

Conflicts of Interest

None to declare.

Supplementary material

12253_2017_341_MOESM1_ESM.doc (28 kb)
ESM 1 (DOC 28 kb)
12253_2017_341_MOESM2_ESM.doc (28 kb)
ESM 2 (DOC 28 kb)


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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Javier Martinez-Useros
    • 1
    Email author
  • Weiyao Li
    • 1
  • Tihomir Georgiev-Hristov
    • 2
  • Maria J. Fernandez-Aceñero
    • 3
  • Aurea Borrero-Palacios
    • 1
  • Nuria Perez
    • 4
  • Angel Celdran
    • 2
  • Jesus Garcia-Foncillas
    • 1
    Email author
  1. 1.Translational Oncology Division, OncoHealth InstituteFundacion Jimenez Diaz University Hospital, Autonomous University of MadridMadridSpain
  2. 2.Hepatobiliary and Pancreatic Surgery Unit, General and Digestive Tract Surgery DepartmentFundacion Jimenez Diaz University HospitalMadridSpain
  3. 3.Department of PathologyClinico San Carlos University HospitalMadridSpain
  4. 4.Department of PathologyUniversity Hospital Fundacion Jimenez DiazMadridSpain

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