Prognostic value of altered N-glycosylation of circulating glycoproteins in patients with unresectable pancreatic cancer treated with gemcitabine.

Pancreas

From the *Departments of Gastroenterology and Hepatology, and †Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama City, Okayama, Japan; ‡Ezose Sciences Inc, Pine Brook, NJ; §Field of Drug Discovery Research, Faculty of Advanced Life Science, Graduate School of Life Science, Hokkaido University; and ∥Medicinal Chemistry Pharmaceuticals, Co, Ltd, Sapporo, Hokkaido, Japan.

Published: May 2015

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Article Abstract

Objectives: The objectives of this study were to examine the whole-serum N-glycan profile of patients with unresectable pancreatic cancer and to evaluate the ability of glycans to predict gemcitabine treatment efficacy and patient survival.

Methods: We collected serum from 52 patients with advanced pancreatic cancer before they began gemcitabine monotherapy. The serum glycan profile was measured through comprehensive quantitative high-throughput glycome analysis and compared with the treatment efficacy and patient survival.

Results: Of the 61 glycans detected, the serum levels of glycan 4310 (molecular weight [m/z] 1549.566), 6301 (m/z 2032.724), and 9200 (m/z 2010.692) were high in patients with a short time to tumor progression (TTP). Multivariate analysis revealed that a high glycan 9200 concentration was an independent risk factor for shorter TTP (hazard ratio, 2.11; 95% confidence interval, 1.07-4.17) and poor overall survival (hazard ratio, 2.56; 95% confidence interval, 1.08-6.19). The median TTP of patients with up-regulation of 9200 after gemcitabine treatment was shorter than for the remaining patients (91 vs 301 days; P = 0.0005). A similar relationship was observed for overall survival (median, 181 vs 561 days; P = 0.001).

Conclusions: Glycan 9200 is a possible biomarker predicting gemcitabine efficacy survival in patients with unresectable pancreatic cancer.

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http://dx.doi.org/10.1097/MPA.0000000000000321DOI Listing

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