File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Methylation of Protocadherin 10, a Novel Tumor Suppressor, Is Associated With Poor Prognosis in Patients With Gastric Cancer

TitleMethylation of Protocadherin 10, a Novel Tumor Suppressor, Is Associated With Poor Prognosis in Patients With Gastric Cancer
Authors
Issue Date2009
Citation
Gastroenterology, 2009, v. 136, n. 2, p. 640-651.e1 How to Cite?
AbstractBackground & Aims: By using methylation-sensitive representational difference analysis, we identified protocadherin 10 (PCDH10), a gene that encodes a protocadherin and is silenced in a tumor-specific manner. We analyzed its epigenetic inactivation, biological effects, and prognostic significance in gastric cancer. Methods: Methylation status was evaluated by combined bisulfite restriction analysis and bisulfite sequencing. The effects of PCDH10 re-expression were determined in growth, apoptosis, proliferation, and invasion assays. PCDH10 target genes were identified by complementary DNA microarray analysis. Results: PCDH10 was silenced or down-regulated in 94% (16 of 17) of gastric cancer cell lines; expression levels were restored by exposure to demethylating agents. Re-expression of PCDH10 in MKN45 gastric cancer cells reduced colony formation in vitro and tumor growth in mice; it also inhibited cell proliferation (P < .01), induced cell apoptosis (P < .001), and repressed cell invasion (P < .05), up-regulating the pro-apoptosis genes Fas, Caspase 8, Jun, and CDKN1A; the antiproliferation gene FGFR; and the anti-invasion gene HTATIP2. PCDH10 methylation was detected in 82% (85 of 104) of gastric tumors compared with 37% (38 of 104) of paired nontumor tissues (P < .0001). In the latter, PCDH10 methylation was higher in precancerous lesions (27 of 45; 60%) than in chronic gastritis samples (11 of 59; 19%) (P < .0001). After a median follow-up period of 16.8 months, multivariate analysis revealed that patients with PCDH10 methylation in adjacent nontumor areas had a significant decrease in overall survival. Kaplan-Meier survival curves showed that PCDH10 methylation was associated significantly with shortened survival in stage I-III gastric cancer patients. Conclusions: PCDH10 is a gastric tumor suppressor; its methylation at early stages of gastric carcinogenesis is an independent prognostic factor. © 2009 AGA Institute.
Persistent Identifierhttp://hdl.handle.net/10722/207020
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170

 

DC FieldValueLanguage
dc.contributor.authorYu, Jun-
dc.contributor.authorCheng, Yuenyee-
dc.contributor.authorTao, Qian-
dc.contributor.authorCheung, Kinfai-
dc.contributor.authorLam, Cleo Nga Yee-
dc.contributor.authorGeng, Hua-
dc.contributor.authorTian, Linwei-
dc.contributor.authorWong, Ying P.-
dc.contributor.authorTong, Joanna-
dc.contributor.authorYing, Jianming-
dc.contributor.authorJin, Hong Chuan-
dc.contributor.authorTo, Kafai-
dc.contributor.authorChan, Francis Ka Leung-
dc.contributor.authorSung, Joseph-
dc.date.accessioned2014-12-09T04:31:15Z-
dc.date.available2014-12-09T04:31:15Z-
dc.date.issued2009-
dc.identifier.citationGastroenterology, 2009, v. 136, n. 2, p. 640-651.e1-
dc.identifier.issn0016-5085-
dc.identifier.urihttp://hdl.handle.net/10722/207020-
dc.description.abstractBackground & Aims: By using methylation-sensitive representational difference analysis, we identified protocadherin 10 (PCDH10), a gene that encodes a protocadherin and is silenced in a tumor-specific manner. We analyzed its epigenetic inactivation, biological effects, and prognostic significance in gastric cancer. Methods: Methylation status was evaluated by combined bisulfite restriction analysis and bisulfite sequencing. The effects of PCDH10 re-expression were determined in growth, apoptosis, proliferation, and invasion assays. PCDH10 target genes were identified by complementary DNA microarray analysis. Results: PCDH10 was silenced or down-regulated in 94% (16 of 17) of gastric cancer cell lines; expression levels were restored by exposure to demethylating agents. Re-expression of PCDH10 in MKN45 gastric cancer cells reduced colony formation in vitro and tumor growth in mice; it also inhibited cell proliferation (P < .01), induced cell apoptosis (P < .001), and repressed cell invasion (P < .05), up-regulating the pro-apoptosis genes Fas, Caspase 8, Jun, and CDKN1A; the antiproliferation gene FGFR; and the anti-invasion gene HTATIP2. PCDH10 methylation was detected in 82% (85 of 104) of gastric tumors compared with 37% (38 of 104) of paired nontumor tissues (P < .0001). In the latter, PCDH10 methylation was higher in precancerous lesions (27 of 45; 60%) than in chronic gastritis samples (11 of 59; 19%) (P < .0001). After a median follow-up period of 16.8 months, multivariate analysis revealed that patients with PCDH10 methylation in adjacent nontumor areas had a significant decrease in overall survival. Kaplan-Meier survival curves showed that PCDH10 methylation was associated significantly with shortened survival in stage I-III gastric cancer patients. Conclusions: PCDH10 is a gastric tumor suppressor; its methylation at early stages of gastric carcinogenesis is an independent prognostic factor. © 2009 AGA Institute.-
dc.languageeng-
dc.relation.ispartofGastroenterology-
dc.titleMethylation of Protocadherin 10, a Novel Tumor Suppressor, Is Associated With Poor Prognosis in Patients With Gastric Cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.gastro.2008.10.050-
dc.identifier.pmid19084528-
dc.identifier.scopuseid_2-s2.0-58649120820-
dc.identifier.volume136-
dc.identifier.issue2-
dc.identifier.spage640-
dc.identifier.epage651.e1-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats