Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer

Sato,Takashi; Soejima,Kenzo; Arai,Eri; Hamamoto,Junko; Yasuda,Hiroyuki; Arai,Daisuke; Ishioka,Kota; Ohgino,Keiko; Naoki,Katsuhiko; Kohno,Takashi; Tsuta,Koji; Watanabe,Shun-Ichi; Kanai,Yae; Betsuyaku,Tomoko

doi:10.3892/or.2015.4082

Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer

Authors:
- Takashi Sato
- Kenzo Soejima
- Eri Arai
- Junko Hamamoto
- Hiroyuki Yasuda
- Daisuke Arai
- Kota Ishioka
- Keiko Ohgino
- Katsuhiko Naoki
- Takashi Kohno
- Koji Tsuta
- Shun-Ichi Watanabe
- Yae Kanai
- Tomoko Betsuyaku
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Affiliations: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Department of Pathology and Clinical Laboratories, Pathology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan, Department of Thoracic Oncology, Thoracic Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
Published online on: June 25, 2015 https://doi.org/10.3892/or.2015.4082
Pages: 1137-1145
Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of the present study was to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LADC). PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with LADC, a major NSCLC subtype. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. PTPRH mRNA expression was significantly upregulated in NSCLC. PTPRH DNA methylation was reduced in LADC samples and inversely correlated with mRNA expression. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P=1.64x10-4) and overall survival (P=5.54x10-5). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P=6.88x10-3). It was confirmed that PTPRH is overexpressed in NSCLC. Furthermore, we determined that PTPRH is epigenetically regulated by DNA hypomethylation, with prognostic implications for LADC.

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