Universität zu Köln

Grimminger, Peter P., Maus, Martin K. H., Schneider, Paul M., Metzger, Ralf, Hoelscher, Arnulf H., Sugita, Hirofumi, Danenberg, Peter V., Alakus, Hakan and Brabender, Jan (2012). Glutathione S-transferase PI (GST-PI) mRNA expression and DNA methylation is involved in the pathogenesis and prognosis of NSCLC. Lung Cancer, 78 (1). S. 87 - 92. CLARE: ELSEVIER IRELAND LTD. ISSN 1872-8332

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Abstract

Introduction: The aim of this study was to investigate the relevance of mRNA expression and DNA methylation of GST-PI in tumor and non-tumor lung tissue from NSCLC patients in terms of prognostic and pathogenetic value of this biomarker. Method: Quantitative real-time PCR was used to measure mRNA expression and DNA methylation of GST-PI in paired tumor (T) and non-tumor (N) lung tissue of 91 NSCLC patients. Of all 91 patients 49% were stage 1,21% stage II and 30% stage IIIA. Forty-seven percent of the patients had squamous cell carcinoma, 36% adenocarcinoma and 17% large cell carcinoma. All patients were R0 resected. Results: GST-PI mRNA expression could be measured in 100% in both (T and N) tissues; GST-PI DNA methylation was detected in 14% (N) and 14% (T). The median GST-PI mRNA expression in N was 7.83 (range: 0.01-19.43) and in T 13.15 (range: 0.01-116.8; p <= 0.001). The median GST-PI methylation was not significantly different between land N. No associations were seen between the mRNA expression or DNA methylation levels and clinical or histopathologic parameters such as gender, age, TNM stage, tumor histology and grading. The median survival of the investigated patients was 59.7 years (the median follow-up was 85.9 months). High GST-PI DNA methylation was significantly associated with a worse prognosis (p = 0.041, log rank test). No correlation was found between the GST-PI DNA methylation levels and the correlating mRNA expression levels. Conclusion: GST-PI mRNA expression seems to be involved in the pathogenesis of NSCLC. High levels of GST-PI DNA methylation in tumor tissue of NSCLC patients have a potential as a biomarker identifying subpopulations with a more aggressive tumor biology. Quantitation of GST-PI DNA methylation may be a useful method to identify patients with a poor prognosis after curative resection and who will benefit from intensive adjuvant therapy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grimminger, Peter P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maus, Martin K. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Paul M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelscher, Arnulf H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sugita, Hirofumi UNSPECIFIED UNSPECIFIED UNSPECIFIED Danenberg, Peter V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Brabender, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482521
DOI:	10.1016/j.lungcan.2012.07.008
Journal or Publication Title:	Lung Cancer
Volume:	78
Number:	1
Page Range:	S. 87 - 92
Date:	2012
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1872-8332
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL LUNG-CANCER; CHI-SQUARE STATISTICS; IMMUNOHISTOCHEMICAL EXPRESSION; SURVIVAL; CHEMOTHERAPY; RESISTANCE; CARCINOMA; LEUKEMIA; MUSTARD; MARKERS Multiple languages Oncology; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48252