Oncotarget

Research Papers:

High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma

Yi-Cheng Lin, Chia-Hung Lin, Yi-Chen Yeh, Hsiang-Ling Ho, Yu-Chung Wu, Mei-Yu Chen and Teh-Ying Chou _

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Oncotarget. 2018; 9:31032-31044. https://doi.org/10.18632/oncotarget.25772

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Abstract

Yi-Cheng Lin1,*, Chia-Hung Lin2,*, Yi-Chen Yeh1, Hsiang-Ling Ho1, Yu-Chung Wu3,4, Mei-Yu Chen2,5 and Teh-Ying Chou1,2,3,5,6

1Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 11221, Taiwan

2Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan

3School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan

4Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11221, Taiwan

5Genome Research Center, National Yang-Ming University, Taipei 11221, Taiwan

6Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Teh-Ying Chou, email: tychou@vghtpe.gov.tw

Mei-Yu Chen, email: meychen@ym.edu.tw

Keywords: lung cancer; OGT; O-GlcNAcylation; EGFR; prognostic marker

Received: December 05, 2017    Accepted: June 25, 2018    Published: July 24, 2018

ABSTRACT

Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge. Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies. O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis. O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA) catalyze O-GlcNAc addition and removal, respectively. We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma. We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035). High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038). Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411–6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183–3.391, P=0.010) in stage I patients. Our findings indicate OGT is a promising biomarker for further classifying early stage lung adenocarcinomas.


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