title: Glutathione S-transferase PI (GST-PI) mRNA expression and DNA methylation is involved in the pathogenesis and prognosis of NSCLC.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 I, 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 T and 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany. peter.grimminger@uk-koeln.de
authors.forename: Peter P
authors.initials: PP
authors.lastname: Grimminger
authors.forename: Martin K H
authors.initials: MK
authors.lastname: Maus
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schneider
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hölscher
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sugita
authors.forename: Peter V
authors.initials: PV
authors.lastname: Danenberg
authors.forename: Hakan
authors.initials: H
authors.lastname: Alakus
authors.forename: Jan
authors.initials: J
authors.lastname: Brabender
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors
chemical_list: D012333:RNA, Messenger; D051549:Glutathione S-Transferase pi