title: Prognostic potential and tumor growth-inhibiting effect of plasma advanced glycation end products in non-small cell lung carcinoma.
abstract: The plasma fluorescence related to the standard fluorescence of advanced glycation end products (AGEs) is a simple measurable blood parameter for distinct diseases but its importance in human cancer, including non-small cell lung carcinoma (NSCLC), is unknown. Plasma samples of 70 NSCLC patients who underwent resection surgery of the tumor were analyzed for the distinct AGE-related fluorescence at 370 nm excitation/440 nm emission. In a retrospective study, we tested the prognostic relevance of this AGE-related plasma fluorescence. The effect of circulating AGEs on the NSCLC growth was studied experimentally in vitro and in vivo. NSCLC patients with high (> median) AGE-related plasma fluorescence were characterized by a later reoccurrence of the tumor after curative surgery and a higher survival rate compared with patients with low plasma fluorescence (25% versus 47% 5-y survival, P = 0.011). Treating NSCLC cell spheroids with patients' plasma showed an inverse correlation between the growth of spheroids in vitro and the individual AGE-related fluorescence of each plasma sample. To confirm the impact of circulating AGEs on the NSCLC progression, we studied the NSCLC growth in mice whose circulating AGE level was elevated by AGE-rich diet. In vivo tumorigenicity assays demonstrated that mice with higher levels of circulating AGEs developed smaller tumors than mice with normal AGE levels. The AGE-related plasma fluorescence has prognostic relevance for NSCLC patients in whom the tumor growth-inhibiting effect of circulating AGEs might play a critical role.
authors.affiliation: Department of Cardio and Thoracic Surgery, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. babett.bartling@medizin.uni-halle.de
authors.forename: Babett
authors.initials: B
authors.lastname: Bartling
authors.forename: Hans-Stefan
authors.initials: HS
authors.lastname: Hofmann
authors.forename: Antonia
authors.initials: A
authors.lastname: Sohst
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hatzky
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
authors.forename: Rolf-Edgar
authors.initials: RE
authors.lastname: Silber
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
mesh_terms: D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology; D045744:Cell Line, Tumor; D004032:Diet; D018450:Disease Progression; D005260:Female; D005453:Fluorescence; D015972:Gene Expression Regulation, Neoplastic; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000737:chemistry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009374:Neoplasms, Experimental / Q000097:blood / Q000473:pathology; D011379:Prognosis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics; D012189:Retrospective Studies; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic