1H NMR-based metabolomics of skin squamous cell carcinoma and peri-tumoral region tissues

Abstract

Squamous cell carcinomas (SCC) are the most frequent forms of skin malignancy. Knowledge of the metabolic changes occur in SCC and peri-tumoral region tissues is still limited. To investigate the metabolic changes in skin SCC and peri-tumoral regions, twenty-four patients with histopathology diagnosis of SCC were included in the study. Tissue samples were obtained from the SCCs, peri-tumoral regions (within 5 mm adjacent to the tumor margin) and distance normal tissues for control (> 5 mm adjacent to the tumor margin) from each patient. The metabolic changes of the three regions were investigated using 1H nuclear magnetic resonance-based metabolomics. Key metabolites in SCC were identified and validated by comparing with the other two regions. Eight metabolites were identified and validated between the SCCs and the controls, the concentrations of lactate, alanine, valine, creatine, aspartate, tyrosine, and glutamine significantly increased in SCC, while that of glucose decreased. The metabolomics analysis showed that lactate and valine were the key metabolites in SCCs and prei-tumoral regions. Pathways analysis showed that valine, leucine, and isoleucine biosynthesis, and pyruvate metabolism were the key abnormal metabolic pathways in SCC. Metabolomics analysis of key metabolites and pathways revealed that glycolysis, tricarboxylic acid (TCA) cycle, and amino acids metabolism played a central role in the metabolic of SCCs and peri-tumoral regions.