Metabolomic\nProfiling of Tumor Tissues Unveils Metabolic\nShifts in Non-Small Cell Lung Cancer Patients with Concurrent Diabetes\nMellitus

A comprehensive understanding of the exact influence\nof type 2\ndiabetes mellitus (T2DM) on the metabolic status of non-small cell\nlung cancer (NSCLC) is still lacking. This study explores metabolic\nalterations in tumor tissues among patients with coexisting NSCLC\nand T2DM in comparison with NSCLC patients. A combined approach of\nclinical analysis and metabolomics was employed, including 20 NSCLC\npatients and 20 NSCLC+T2DM patients. Targeted metabolomics analysis\nwas performed on tumor tissues using the liquid chromatography–mass\nspectrometry (LC-MS) approach. A clear segregation was observed between\nNSCLC+T2DM and matched NSCLC tissue samples in Orthogonal Partial\nLeast Squares Discrimination Analysis (OPLS-DA). Furthermore, the\nlevels of 7 metabolites are found to be significantly different between\ndiabetes/nondiabetes tumor tissue samples. The related pathways included\narginine biosynthesis, glutathione metabolism, arginine and proline\nmetabolism, purine metabolism, biotin metabolism, and histidine metabolism.\n3-Phenyllactic acid, carnitine-C5, carnitine-C12, and serotonin showed\na positive linear correlation with fasting blood glucose levels in\nNSCLC patients. Uridine, pipecolic acid, cytosine, and fasting blood\nglucose levels were found to have a negative correlation. Our results\nsuggest that NSCLC patients with concurrent T2DM exhibit distinct\nmetabolic shifts in tumor tissues compared to those of solely NSCLC\npatients.