Studying the mechanism underlying lipid metabolism in osteosarcoma based on transcriptomic RNA-seq and single-cell data.

BACKGROUND: We aimed to provide a new typing method for Osteosarcoma (OS) based on single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the perspective of lipid metabolism and examine its potential mechanisms in the onset and progression of OS.

METHODS: Scores for six lipid metabolic pathways were calculated by single-sample gene set enrichment analysis (ssGSEA) based on a scRNA-seq dataset and three microarray expression profiles. Subsequently, cluster typing was conducted using unsupervised consistency clustering. Further, single-cell clustering and dimensionality-reduction analyses identified cell subtypes. Finally, an analysis of cellular receptors was performed using CellphoneDB to identify cellular communication.

RESULTS: OS was classified into three subtypes based on lipid metabolic pathways. Among them, patients in clust3 showed poor prognoses, whereas those in clust1 and 2 exhibited good prognoses. In addition, ssGSEA analysis showed that patients in clust3 had lower immune cell scores. Moreover, the Th17 cell differentiation pathway was significantly differentially enriched between clust2 and 3, with lower enrichment scores for metabolic pathways in the former relative to clust1 and 2. A total of 24 genes were up-regulated between clust1 and 2, while 20 were down-regulated in clust3. These observations were validated by single-cell data analysis. Finally, through scRNA-seq data analysis, we identified nine ligand-receptor pairs particularly critical for communication between normal and malignant cells.

CONCLUSION: 3 clusters were identified and the single-cell analysis revealed that malignant cells dominated lipid metabolism patterns in tumors, thereby influencing the tumor microenvironment (TME).