Skip to main content
Top
Published in: BMC Gastroenterology 1/2013

Open Access 01-12-2013 | Research article

Correlation between the methylation of SULF2 and WRN promoter and the irinotecan chemosensitivity in gastric cancer

Authors: Lin Wang, Li Xie, Jun Wang, Jie Shen, Baorui Liu

Published in: BMC Gastroenterology | Issue 1/2013

Login to get access

Abstract

Background

At present, no study has compared the correlation between SULF2, WRN promoter methylation and clinicopathological parameters of patients with gastric cancer and the sensitivity to irinotecan (CPT-11).

Methods

We collected 102 fresh tumor tissues from pathologically diagnosed gastric carcinoma patients. Methylation specific PCR was used to detect the promoter methylation of SULF2 and WRN. The chemosensitivity of irinotecan to gastric tomor was tested by MTT. Then we compared the chemosensitivity difference of the methylated group with unmethylated group.

Results

The rates of SULF2, WRN methylation were 28.3% (29/102) and 23.6% (24/102), separately. Patients with SULF2 methylation were more sensitive to CPT-11 than those without SULF2 methylation (P < 0.01). Patients with both SULF2 and WRN methylation were also more sensitive to CPT-11 than others ( P < 0.05).

Conclusion

SULF2 and WRN promoter methylation detection indicates potential predictive biomarkers to identify and target the most sensitive gastric cancer subpopulation for personalized CPT-11 therapy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed
2.
go back to reference Fadi SF: A general review of the role of irinotecan (CPT11) in the treatment of gastric cancer. Med Oncol. 2007, 24: 137-146. 10.1007/BF02698032.CrossRef Fadi SF: A general review of the role of irinotecan (CPT11) in the treatment of gastric cancer. Med Oncol. 2007, 24: 137-146. 10.1007/BF02698032.CrossRef
3.
go back to reference Tessema M, Yingling CM, Thomaa CL, et al: SULF2 methylation is prognostic for lung cancer survival and increases sensitivity to topoisomerase-I inhibitors via induction of ISG15. Oncogene. 2011, 12: 1-10. Tessema M, Yingling CM, Thomaa CL, et al: SULF2 methylation is prognostic for lung cancer survival and increases sensitivity to topoisomerase-I inhibitors via induction of ISG15. Oncogene. 2011, 12: 1-10.
4.
go back to reference Agrelo R, Cheng WH, Fernando S, et al: Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl Acad Sci U S A. 2006, 103: 8823-8827.CrossRef Agrelo R, Cheng WH, Fernando S, et al: Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl Acad Sci U S A. 2006, 103: 8823-8827.CrossRef
5.
go back to reference Yoshimasu T, Oura S, Hirai I, et al: Data acquisition for the histoculture drug response assay in lung cancer. J Thorac Cardiovasc Surg. 2007, 133: 303-308. 10.1016/j.jtcvs.2006.06.030.CrossRefPubMed Yoshimasu T, Oura S, Hirai I, et al: Data acquisition for the histoculture drug response assay in lung cancer. J Thorac Cardiovasc Surg. 2007, 133: 303-308. 10.1016/j.jtcvs.2006.06.030.CrossRefPubMed
6.
go back to reference TETSURO K: Chemotherapy strategies for gastric cancer. In Vivo. 2008, 22: 273-278. TETSURO K: Chemotherapy strategies for gastric cancer. In Vivo. 2008, 22: 273-278.
7.
go back to reference Das PM, Singal R: DNA methylation and cancer. J Clin Oncol. 2004, 22: 4632-4642. 10.1200/JCO.2004.07.151.CrossRefPubMed Das PM, Singal R: DNA methylation and cancer. J Clin Oncol. 2004, 22: 4632-4642. 10.1200/JCO.2004.07.151.CrossRefPubMed
8.
go back to reference Rashid A, Issa JP: CpG island methylation in gastroenterologic neoplasia: a maturing field. Gastroenterology. 2004, 127: 1578-1588. 10.1053/j.gastro.2004.09.007.CrossRefPubMed Rashid A, Issa JP: CpG island methylation in gastroenterologic neoplasia: a maturing field. Gastroenterology. 2004, 127: 1578-1588. 10.1053/j.gastro.2004.09.007.CrossRefPubMed
9.
go back to reference Uchimura K, Morimoto-Tomita M, Bistrup A, et al: Sulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1. BMC Biochem. 2006, 7: 2-14. 10.1186/1471-2091-7-2.CrossRefPubMedPubMedCentral Uchimura K, Morimoto-Tomita M, Bistrup A, et al: Sulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1. BMC Biochem. 2006, 7: 2-14. 10.1186/1471-2091-7-2.CrossRefPubMedPubMedCentral
10.
go back to reference Lai JP, Sandhu DS, Yu C, Han T, Moser CD, Jackson KK, et al: Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma. Hepatology. 2008, 47: 1211-1222. 10.1002/hep.22202.CrossRefPubMedPubMedCentral Lai JP, Sandhu DS, Yu C, Han T, Moser CD, Jackson KK, et al: Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma. Hepatology. 2008, 47: 1211-1222. 10.1002/hep.22202.CrossRefPubMedPubMedCentral
11.
go back to reference Morimoto-Tomita M, Uchimura K, Bistrup A, Lum DH, Egeblad M, Boudreau N, et al: Sulf-2, a proangiogenic heparin sulfate endosulfatase, is upregulated in breast cancer. Neoplasia. 2005, 7: 1001-1010. 10.1593/neo.05496.CrossRefPubMedPubMedCentral Morimoto-Tomita M, Uchimura K, Bistrup A, Lum DH, Egeblad M, Boudreau N, et al: Sulf-2, a proangiogenic heparin sulfate endosulfatase, is upregulated in breast cancer. Neoplasia. 2005, 7: 1001-1010. 10.1593/neo.05496.CrossRefPubMedPubMedCentral
12.
go back to reference Lemjabbar-Alaoui H, van Zante A, Singer MS, Xue Q, Wang YQ, Tsay D, et al: Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis. Oncogene. 2010, 29: 635-646. 10.1038/onc.2009.365.CrossRefPubMed Lemjabbar-Alaoui H, van Zante A, Singer MS, Xue Q, Wang YQ, Tsay D, et al: Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis. Oncogene. 2010, 29: 635-646. 10.1038/onc.2009.365.CrossRefPubMed
13.
go back to reference Desai SD, Wood LM, Tsai YC, et al: ISG15 as a novel tumor biomarker for drug sensitivity. Mol Cancer Ther. 2008, 7: 1430-1439. 10.1158/1535-7163.MCT-07-2345.CrossRefPubMedPubMedCentral Desai SD, Wood LM, Tsai YC, et al: ISG15 as a novel tumor biomarker for drug sensitivity. Mol Cancer Ther. 2008, 7: 1430-1439. 10.1158/1535-7163.MCT-07-2345.CrossRefPubMedPubMedCentral
14.
go back to reference Tessema M, Yu YY, Stidley CA, Machida EO, Schuebel KE, Baylin SB, et al: Concomitant promoter methylation of multiple genes in lung adenocarcinomas from current, former and never smokers. Carcinogenesis. 2009, 30: 1132-1138. 10.1093/carcin/bgp114.CrossRefPubMedPubMedCentral Tessema M, Yu YY, Stidley CA, Machida EO, Schuebel KE, Baylin SB, et al: Concomitant promoter methylation of multiple genes in lung adenocarcinomas from current, former and never smokers. Carcinogenesis. 2009, 30: 1132-1138. 10.1093/carcin/bgp114.CrossRefPubMedPubMedCentral
15.
go back to reference Agrelo R, Cheng WH, Setien F, et al: Epigenetic inactivation of the premature aging Werner syn-drome gene in human cancer. Proc Natl Acad Sci U S A. 2006, 103: 8822-8827. 10.1073/pnas.0600645103.CrossRefPubMedPubMedCentral Agrelo R, Cheng WH, Setien F, et al: Epigenetic inactivation of the premature aging Werner syn-drome gene in human cancer. Proc Natl Acad Sci U S A. 2006, 103: 8822-8827. 10.1073/pnas.0600645103.CrossRefPubMedPubMedCentral
16.
go back to reference Wen-Hsing C, Rika K, Patricia L, Opresko : Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links. Nucleic Acids Res. 2006, 34: 92751-92760. Wen-Hsing C, Rika K, Patricia L, Opresko : Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links. Nucleic Acids Res. 2006, 34: 92751-92760.
17.
go back to reference Monika A, Joshua A, Sommers , Robert H: Hoemaker, inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress. Proc Natl Acad Sci U S A. 2011, 108 (40): 1525-1530. Monika A, Joshua A, Sommers , Robert H: Hoemaker, inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress. Proc Natl Acad Sci U S A. 2011, 108 (40): 1525-1530.
18.
go back to reference Furukawa T, Kubota T, Hoffman RM: Clinical applications of the histoculture drug response assay. Clin Cancer Res. 1995, 1: 305-311.PubMed Furukawa T, Kubota T, Hoffman RM: Clinical applications of the histoculture drug response assay. Clin Cancer Res. 1995, 1: 305-311.PubMed
19.
go back to reference Hayashi Y, Kuriyama H, Umezu H, Tanaka J, Yoshimasu T, Furukawa T: Class III beta-tubulin expression in tumor cells is correlated with resistance to docetaxel in patients with completely resected non-small-cell lung cancer. InternMed. 2009, 48: 203-208. Hayashi Y, Kuriyama H, Umezu H, Tanaka J, Yoshimasu T, Furukawa T: Class III beta-tubulin expression in tumor cells is correlated with resistance to docetaxel in patients with completely resected non-small-cell lung cancer. InternMed. 2009, 48: 203-208.
20.
go back to reference Koopman M, Knijn N, Richman S, et al: The correlation between topoisomerase-I (Topo1) expression and outcome of treatment with capecitabine and irinotecan in advanced colorectal cancer (ACC) patients (pts) treated in the CAIRO study of the Dutch Colorectal Cancer Group (DCCG). Eur J Cancer. 2009, 7: 321-325.CrossRef Koopman M, Knijn N, Richman S, et al: The correlation between topoisomerase-I (Topo1) expression and outcome of treatment with capecitabine and irinotecan in advanced colorectal cancer (ACC) patients (pts) treated in the CAIRO study of the Dutch Colorectal Cancer Group (DCCG). Eur J Cancer. 2009, 7: 321-325.CrossRef
21.
go back to reference Hoskins JM, Marcuello E, Altes A, et al: Irinotecan pharmacogenetics: influence of pharmacodynamic genes. Clin Cancer Re. 2008, 14: 1788-1796. 10.1158/1078-0432.CCR-07-1472.CrossRef Hoskins JM, Marcuello E, Altes A, et al: Irinotecan pharmacogenetics: influence of pharmacodynamic genes. Clin Cancer Re. 2008, 14: 1788-1796. 10.1158/1078-0432.CCR-07-1472.CrossRef
22.
go back to reference Higinio D, Silvia ML, Elena E, et al: Aprataxin tumor levels predict response of colorectal cancer patients to irinotecan-based treatment. Clin Cancer Res. 2010, 16 (8): 2375-2382. 10.1158/1078-0432.CCR-09-3275.CrossRef Higinio D, Silvia ML, Elena E, et al: Aprataxin tumor levels predict response of colorectal cancer patients to irinotecan-based treatment. Clin Cancer Res. 2010, 16 (8): 2375-2382. 10.1158/1078-0432.CCR-09-3275.CrossRef
Metadata
Title
Correlation between the methylation of SULF2 and WRN promoter and the irinotecan chemosensitivity in gastric cancer
Authors
Lin Wang
Li Xie
Jun Wang
Jie Shen
Baorui Liu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2013
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-13-173

Other articles of this Issue 1/2013

BMC Gastroenterology 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.