title: Increased phosphatidylethanolamine N-methyltransferase gene expression in non-small-cell lung cancer tissue predicts shorter patient survival.
abstract: Lipid mobilization is of great importance for tumor growth and studies have suggested that cancer cells exhibit abnormal choline phospholipid metabolism. In the present study, we hypothesized that phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is increased in non-small-cell lung cancer (NSCLC) tissues and that increased gene expression acts as a predictor of shorter patient survival. Forty-two consecutive patients with resected NSCLC were enrolled in this study. Paired samples of lung cancer tissues and adjacent non-cancer lung tissues were collected from resected specimens for the estimation ofPEMTexpression. SYBR Green-based real-time polymerase chain reaction was used for quantification of PEMT mRNA in lung cancer tissues. Lipoprotein lipase (LPL) and fatty acid synthase (FASN) activities had already been measured in the same tissues. During a four-year follow-up, 21 patients succumbed to tumor progression. One patient did not survive due to non-cancer reasons and was not included in the analysis. Cox regression analysis was used to assess the prognostic value ofPEMTexpression. Our findings show that elevatedPEMTexpression in the cancer tissue, relative to that in the adjacent non-cancer lung tissue, predicts shorter patient survival independently of standard prognostic factors and also independently of increased LPL or FASN activity, the two other lipid-related predictors of shorter patient survival. These findings suggest that active phosphatidylcholine and/or choline metabolism are essential for tumor growth and progression.
authors.affiliation: Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: David
authors.initials: D
authors.lastname: Zinrajh
authors.affiliation: Department of Physiological Chemistry, Center for Physiological Medicine, Medical University of Graz, A-8010 Graz, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Hörl
authors.affiliation: Department of Physiological Chemistry, Center for Physiological Medicine, Medical University of Graz, A-8010 Graz, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Jürgens
authors.affiliation: Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
authors.affiliation: Department of Thoracic Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: Miha
authors.initials: M
authors.lastname: Sok
authors.affiliation: Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: Darko
authors.initials: D
authors.lastname: Cerne
keywords: fatty acid synthase; gene expression; lipoprotein lipase; lung cancer tissue; phosphatidylethanolamine N-methyltransferase; survival analysis