Prognostic Implication of PTPRH Hypomethylation in Non-small Cell Lung Cancer

Overview

Journal Oncol Rep

Specialty Oncology

Date 2015 Jul 3

PMID 26134684

Citations 16

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

Affiliations

Soon will be listed here.

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.

Citing Articles

PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway.

Wang S, Cheng Z, Cui Y, Xu S, Luan Q, Jing S J Transl Med. 2023; 21(1):819.

PMID: 37974250 PMC: 10652596. DOI: 10.1186/s12967-023-04703-5.

A Systematic Review of Progress toward Unlocking the Power of Epigenetics in NSCLC: Latest Updates and Perspectives.

Sulewska A, Pilz L, Manegold C, Ramlau R, Charkiewicz R, Niklinski J Cells. 2023; 12(6).

PMID: 36980246 PMC: 10047383. DOI: 10.3390/cells12060905.

Aberrant Methylation of the Imprinted C19MC and MIR371-3 Clusters in Patients with Non-Small Cell Lung Cancer.

Boyero L, Noguera-Ucles J, Castillo-Pena A, Salinas A, Sanchez-Gastaldo A, Alonso M Cancers (Basel). 2023; 15(5).

PMID: 36900258 PMC: 10000578. DOI: 10.3390/cancers15051466.

Molecular Typing Based on Oxidative Stress Genes and Establishment of Prognostic Characteristics of 7 Genes in Lung Adenocarcinoma.

Tu J, Tang M, Li G, Chen L, Huang Y Oxid Med Cell Longev. 2022; 2022:9683819.

PMID: 36148413 PMC: 9485712. DOI: 10.1155/2022/9683819.

Elevated phosphorylation of EGFR in NSCLC due to mutations in PTPRH.

Swiatnicki M, Rennhack J, Ortiz M, Hollern D, Perry A, Kubiak R PLoS Genet. 2022; 18(9):e1010362.

PMID: 36054194 PMC: 9477422. DOI: 10.1371/journal.pgen.1010362.

References

Oka T, Ouchida M, Koyama M, Ogama Y, Takada S, Nakatani Y . Gene silencing of the tyrosine phosphatase SHP1 gene by aberrant methylation in leukemias/lymphomas. Cancer Res. 2002; 62(22):6390-4. View

Motiwala T, Majumder S, Kutay H, Smith D, Neuberg D, Lucas D . Methylation and silencing of protein tyrosine phosphatase receptor type O in chronic lymphocytic leukemia. Clin Cancer Res. 2007; 13(11):3174-81. PMC: 3074612. DOI: 10.1158/1078-0432.CCR-06-1720. View

Koyama M, Oka T, Ouchida M, Nakatani Y, Nishiuchi R, Yoshino T . Activated proliferation of B-cell lymphomas/leukemias with the SHP1 gene silencing by aberrant CpG methylation. Lab Invest. 2003; 83(12):1849-58. DOI: 10.1097/01.lab.0000106503.65258.2b. View

Motiwala T, Kutay H, Ghoshal K, Bai S, Seimiya H, Tsuruo T . Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer. Proc Natl Acad Sci U S A. 2004; 101(38):13844-9. PMC: 518843. DOI: 10.1073/pnas.0405451101. View

Matozaki T, Suzuki T, Uchida T, Inazawa J, Ariyama T, Matsuda K . Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and its expression in gastrointestinal cancers. J Biol Chem. 1994; 269(3):2075-81. View

Seo Y, Matozaki T, Tsuda M, Hayashi Y, Itoh H, Kasuga M . Overexpression of SAP-1, a transmembrane-type protein tyrosine phosphatase, in human colorectal cancers. Biochem Biophys Res Commun. 1997; 231(3):705-11. DOI: 10.1006/bbrc.1997.6139. View

Reddy J, Shivapurkar N, Takahashi T, Parikh G, Stastny V, Echebiri C . Differential methylation of genes that regulate cytokine signaling in lymphoid and hematopoietic tumors. Oncogene. 2004; 24(4):732-6. DOI: 10.1038/sj.onc.1208032. View

Jurinke C, Denissenko M, Oeth P, Ehrich M, Van Den Boom D, Cantor C . A single nucleotide polymorphism based approach for the identification and characterization of gene expression modulation using MassARRAY. Mutat Res. 2005; 573(1-2):83-95. DOI: 10.1016/j.mrfmmm.2005.01.007. View

Walchli S, Espanel X, Hooft van Huijsduijnen R . Sap-1/PTPRH activity is regulated by reversible dimerization. Biochem Biophys Res Commun. 2005; 331(2):497-502. DOI: 10.1016/j.bbrc.2005.03.196. View

10.

van Doorn R, Zoutman W, Dijkman R, de Menezes R, Commandeur S, Mulder A . Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol. 2005; 23(17):3886-96. DOI: 10.1200/JCO.2005.11.353. View

11.

Wang J, Dai D . Metastatic suppressor genes inactivated by aberrant methylation in gastric cancer. World J Gastroenterol. 2007; 13(43):5692-8. PMC: 4171254. DOI: 10.3748/wjg.v13.i43.5692. View

12.

Sadakata H, Okazawa H, Sato T, Supriatna Y, Ohnishi H, Kusakari S . SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis. Genes Cells. 2009; 14(3):295-308. DOI: 10.1111/j.1365-2443.2008.01270.x. View

13.

Veeriah S, Brennan C, Meng S, Singh B, Fagin J, Solit D . The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers. Proc Natl Acad Sci U S A. 2009; 106(23):9435-40. PMC: 2687998. DOI: 10.1073/pnas.0900571106. View

14.

Heller G, Zielinski C, Zochbauer-Muller S . Lung cancer: from single-gene methylation to methylome profiling. Cancer Metastasis Rev. 2010; 29(1):95-107. DOI: 10.1007/s10555-010-9203-x. View

15.

Noguchi T, Tsuda M, Takeda H, Takada T, Inagaki K, Yamao T . Inhibition of cell growth and spreading by stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1) through dephosphorylation of p130cas. J Biol Chem. 2001; 276(18):15216-24. DOI: 10.1074/jbc.M007208200. View

16.

Takada T, Noguchi T, Inagaki K, Hosooka T, Fukunaga K, Yamao T . Induction of apoptosis by stomach cancer-associated protein-tyrosine phosphatase-1. J Biol Chem. 2002; 277(37):34359-66. DOI: 10.1074/jbc.M206541200. View

17.

Matozaki T, Murata Y, Mori M, Kotani T, Okazawa H, Ohnishi H . Expression, localization, and biological function of the R3 subtype of receptor-type protein tyrosine phosphatases in mammals. Cell Signal. 2010; 22(12):1811-7. DOI: 10.1016/j.cellsig.2010.07.001. View

18.

Julien S, Dube N, Hardy S, Tremblay M . Inside the human cancer tyrosine phosphatome. Nat Rev Cancer. 2010; 11(1):35-49. DOI: 10.1038/nrc2980. View

19.

Baylin S, Jones P . A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011; 11(10):726-34. PMC: 3307543. DOI: 10.1038/nrc3130. View

20.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View