Exploring glycerophospholipid metabolism in nasopharyngeal carcinoma: interactions between malignant epithelial cells and CCL11-expressing fibroblasts

<h4>Background</h4>Nasopharyngeal carcinoma (NPC) is associated with aberrant cellular metabolism and interactions between tumor and stromal cells. This study aims to elucidate the role of glycerophospholipid metabolism in NPC, particularly focusing on the interplay between malignant epithelial cells and fibroblasts.<h4>Methods</h4>We employed a multi-omics approach integrating single-cell transcriptomics, 10x spatial transcriptomics, and spatial metabolomics to analyze the gene expression and metabolite profiles in NPC tissues. Differential metabolite abundance and gene expression were evaluated to identify key glycerophospholipid-related genes.<h4>Results</h4>We identified five glycerophospholipid-related genes-AGPAT3, DGAT2, SLC44A1, AGPAT5, and LPGAT1-that were significantly upregulated in NPC and EBER+ tumor-enriched regions. Fibroblasts expressing CCL11 were found to be associated with fatty acid accumulation and potentially with enhanced glycerophospholipid metabolism through interactions with malignant epithelial cells. Additionally, spatial trajectory analysis indicated shared and distinct gene expression patterns during differentiation toward peritumoral and intratumoral immune regions, revealing a complex landscape of NPC invasion.<h4>Conclusion</h4>Our findings suggest that glycerophospholipid metabolism may play an important role in NPC progression and highlight the potential of AGPAT3, DGAT2, SLC44A1, AGPAT5, and LPGAT1 as diagnostic and prognostic markers. This study provides novel insights into the metabolic interactions within the NPC microenvironment, providing insights for potential targeted therapeutic interventions.