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03.11.2017 | Original Article

Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients

verfasst von: Javier Martinez-Useros, Weiyao Li, Tihomir Georgiev-Hristov, Maria J. Fernandez-Aceñero, Aurea Borrero-Palacios, Nuria Perez, Angel Celdran, Jesus Garcia-Foncillas

Erschienen in: Pathology & Oncology Research | Ausgabe 1/2019

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Abstract

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.

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Titel: Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients
verfasst von: Javier Martinez-Useros
Weiyao Li
Tihomir Georgiev-Hristov
Maria J. Fernandez-Aceñero
Aurea Borrero-Palacios
Nuria Perez
Angel Celdran
Jesus Garcia-Foncillas
Publikationsdatum: 03.11.2017
Verlag: Springer Netherlands
Erschienen in: Pathology & Oncology Research / Ausgabe 1/2019
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-017-0341-0

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Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients

Abstract

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