Single-cell and spatial transcriptomics reveal an arachidonic acid-related cellular atlas in lung adenocarcinoma.

PURPOSE: Arachidonic acid (AA), a membrane-abundant polyunsaturated fatty acid, is primarily liberated from membrane phospholipids by phospholipase A2 (PLA2), and is subsequently metabolized into bioactive eicosanoids involved in vascular tone and inflammation. With lipidomics advances, AA metabolism's multifaceted roles in the tumor microenvironment (TME) have emerged, and it is recognized as a key driver and potential therapeutic axis in lung adenocarcinoma (LUAD). We utilized spatial transcriptomics sequencing (ST-seq) and LUAD-associated single-cell RNA sequencing (scRNA-seq) to explore crucial AA-related biomarkers in LUAD.

PATIENTS AND

METHODS

ScRNA-seq and ST-seq data underwent quality control, integration, clustering, and annotation. Cellular communication analysis explored TME cell/regional regulatory links. Differential cell populations were identified between primary tumor and normal groups; key cells were selected via enrichment pathways and communication patterns. Biomarkers were chosen through differential expression analysis and protein-protein interaction (PPI) network, followed by enrichment analysis, molecular/drug network construction, key cell re-clustering, and pseudotime analysis.

RESULTS

Twelve cell types were identified in scRNA-seq, with T cells and epithelial cells among the top three. ST-seq revealed LUAD tissues comprise cancer, lymph, normal epithelium, and stroma regions. T cells and epithelial cells had extensive intercellular connections, designated as key cells. PTGS2, TBXAS1, AKR1C3, and HPGD were selected as biomarkers via PPI network. Re-clustering and pseudotime analysis showed most LUAD epithelial cells and T cells were terminally differentiated; PTGS2 and HPGD expression rose then declined in the middle-late stages of epithelial cell subpopulation differentiation.

CONCLUSION

In this study, we observed the crucial functions of T cells and epithelial cells as well as AA-related biomarkers PTGS2, TBXAS1, AKR1C3, and HPGD in LUAD. These findings provide mechanistic context and suggest testable biomarkers for future translational studies.