Spatial Metabolomics and Transcriptomics Reveal Metabolic Reprogramming and Cellular Interactions in Nasopharyngeal...

Area of Science:

• Oncology
• Metabolomics
• Transcriptomics
• Cancer Biology

Background:

• Nasopharyngeal carcinoma (NPC) exhibits variable treatment responses, necessitating molecular insights.
• Understanding the tumor microenvironment (TME) and metabolic reprogramming is crucial for improving NPC therapy.

Purpose of the Study:

• To explore spatial metabolic and gene expression alterations in NPC related to therapeutic response and PD-1 levels.
• To identify molecular players influencing treatment outcomes in NPC.

Main Methods:

• Spatial metabolomics (SM) and spatial transcriptomics (ST) were employed.
• Investigated metabolic pathways, metabolites, cell types, and interactions within the TME.
• Validated prognostic targets using TCGA datasets and in vitro functional analyses.

Main Results:

• Significant metabolic reprogramming in lipid, branched-chain amino acid (BCAA), and glutamine metabolism was observed.
• Six key BCAA metabolism genes (IL4I1, OXCT1, BCAT2, DLD, ALDH1B1, HADH) distinguished treatment-sensitive from resistant NPC.
• Gene silencing of DLD or IL4I1 inhibited NPC proliferation, invasion, and induced cell cycle arrest.

Conclusions:

• Key molecular players in BCAA metabolism are pivotal for NPC therapeutic response.
• These genes serve as potential prognostic biomarkers and therapeutic targets for precision oncology in NPC.
• Findings contribute to strategies for improving NPC patient outcomes.