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

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish
Pages (from-to)1137-1145
Number of pages9
JournalOncology Reports
Issue number3
StatePublished - 1 Sep 2015
Externally publishedYes


  • DNA methylation
  • Hypomethylation
  • Non-small cell lung cancer
  • Prognostic factor


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