Metabolomic Profiling of Tumor Tissues Unveils Metabolic Shifts in Non-Small Cell Lung Cancer Patients with Concurrent Diabetes Mellitus

J Proteome Res. 2024 Sep 6;23(9):3746-3753. doi: 10.1021/acs.jproteome.3c00924. Epub 2024 Aug 20.

Abstract

A comprehensive understanding of the exact influence of type 2 diabetes mellitus (T2DM) on the metabolic status of non-small cell lung cancer (NSCLC) is still lacking. This study explores metabolic alterations in tumor tissues among patients with coexisting NSCLC and T2DM in comparison with NSCLC patients. A combined approach of clinical analysis and metabolomics was employed, including 20 NSCLC patients and 20 NSCLC+T2DM patients. Targeted metabolomics analysis was performed on tumor tissues using the liquid chromatography-mass spectrometry (LC-MS) approach. A clear segregation was observed between NSCLC+T2DM and matched NSCLC tissue samples in Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA). Furthermore, the levels of 7 metabolites are found to be significantly different between diabetes/nondiabetes tumor tissue samples. The related pathways included arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, purine metabolism, biotin metabolism, and histidine metabolism. 3-Phenyllactic acid, carnitine-C5, carnitine-C12, and serotonin showed a positive linear correlation with fasting blood glucose levels in NSCLC patients. Uridine, pipecolic acid, cytosine, and fasting blood glucose levels were found to have a negative correlation. Our results suggest that NSCLC patients with concurrent T2DM exhibit distinct metabolic shifts in tumor tissues compared to those of solely NSCLC patients.

Keywords: diabetes; metabolites; metabolomics; non-small cell lung cancer.

MeSH terms

  • Aged
  • Arginine / metabolism
  • Blood Glucose / metabolism
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carnitine / analogs & derivatives
  • Carnitine / metabolism
  • Chromatography, Liquid
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / metabolism
  • Female
  • Humans
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Mass Spectrometry
  • Metabolome
  • Metabolomics* / methods
  • Middle Aged

Substances

  • Blood Glucose
  • Carnitine
  • Arginine