title: Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer.
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.
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Soejima
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Arai
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hamamoto
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Arai
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Ishioka
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohgino
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naoki
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Pathology and Clinical Laboratories, Pathology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.affiliation: Department of Thoracic Oncology, Thoracic Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Shun-Ichi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C431695:PTPRH protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3