Prognostic Potential and Tumor Growth-Inhibiting Effect of Plasma Advanced Glycation End Products in Non-Small Cell Lung Carcinoma
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.
The authors thank Renate Donath, Stephanie Tuche and Sabine Koitzsch for technical assistance and Peter Schmidt (Medical Faculty, Halle [Saale]) for clinical assistance. We also thank Gesine Hansen (Hannover Medical School, Germany), Stefan Burdach (Technical University Munich, Germany) and Vesselin Christov (Medical Faculty, Halle [Saale]) for cooperation with the microarray analysis. This study was supported by Deutsche Krebshilfe (107078), Deutsche Forschungsgemeinschaft (Si-1317/1-1) and Wilhelm Roux grants (FKZ 7/04, FKZ14/14).
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