Oncotarget

Clinical Research Papers:

GOT1/AST1 expression status as a prognostic biomarker in pancreatic ductal adenocarcinoma

Fenja M Feld _, Philipp D Nagel, Stephanie E Weissinger, Claudia Welke, Albrecht Stenzinger, Peter Möller and Jochen K Lennerz

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Oncotarget. 2015; 6:4516-4526. https://doi.org/10.18632/oncotarget.2799

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Abstract

Fenja M Feld1, Philipp D Nagel1, Stephanie E Weissinger1, Claudia Welke2, Albrecht Stenzinger3, Peter Möller1, Jochen K Lennerz1

1Institute of Pathology, University Ulm 89081, Germany

2Comprehensive Cancer Center Ulm, University Hospital Ulm 89081, Germany

3University Hospital Heidelberg, Department of Pathology, University Heidelberg 69120, Germany

Correspondence to:

Jochen K. Lennerz, e-mail: jochen.lennerz@uni-ulm.de

Keywords: pancreatic cancer, glutamic oxaloacetatic transaminase 1, KRAS, PDAC, biomarker

Received: October 14, 2014     Accepted: November 20, 2014     Published: February 19, 2015

ABSTRACT

Prognostication in pancreatic ductal adenocarcinoma (PDAC) remains a challenge. Recently, a link between mutated KRAS and glutamic-oxaloacetic transaminase (GOT1/AST1) has been described as part of the metabolic reprogramming in PDAC. The clinical relevance of this novel metabolic KRAS-GOT1 link has not been determined in primary human patient samples. Here we studied the GOT1 expression status as a prognostic biomarker in PDAC. We employed three independent PDAC cohorts with clinicopathological- and follow-up data: a) ICGC, comprising 57 patients with whole-exome sequencing and genome-wide expression profiling; b) ULM, composed of 122 surgically-treated patients with tissue-samples and KRAS status; c) a validation cohort of 140 primary diagnostic biopsy samples. GOT1 expression was assessed by RNA level (ICGC) or immunolabeling (ULM/validation cohort). GOT1 expression varied (ICGC) and correlation with the KRAS mutation- and expression status was imperfect (P = 0.2, ICGC; P = 0.8, ULM). Clinicopathological characteristics did not differ when patients were separated based on GOT1 high vs. low (P = 0.08–1.0); however, overall survival was longer in patients with GOT1-expressing tumors (P = 0.093, ICGC; P = 0.049, ULM). Multivariate analysis confirmed GOT1 as an independent prognostic marker (P = 0.009). Assessment in univariate (P = 0.002) and multivariate models in the validation cohort (P = 0.019), containing 66% stage IV patients, confirmed the independency of GOT1.

We propose the GOT1 expression status as a simple and reliable prognostic biomarker in pancreatic ductal adenocarcinoma.


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