肝细胞癌肿瘤边界代谢空间异质性研究OA

Objective To explore the spatial heterogeneity of tumor boundary tissue metabolism in hepatocellular carcinoma(HCC)patients using time-of-flight secondary ion mass spectrometry(TOF-SIMS),and to analyze the characteristics of key metabolites in spatial distribution.Methods After obtaining adjacent non-tumor tissue samples from HCC patients,the samples were snap-frozen and embedded.Serial tissue sections were prepared using frozen section technology,and spatial metabolomic analysis was performed on the tissue sections using TOF-SIMS.The mass spectrometry data were clustered and spatially mapped at the single-cell level using the SEAM algorithm.Results TOF-SIMS combined with the SEAM algorithm successfully achieved high-resolution spatial metabolomic analysis of HCC boundary tissue.The results showed significant metabolic heterogeneity between the intra-and extra-tumoral regions,as well as within the tumor parenchyma,which could be subdivided into two cell subpopulations with different metabolic characteristics.Differential metabolite analysis identified two key phosphate-related ions(m/z=62.97 and m/z=78.96).Quantitative spatial distribution studies revealed that cell populations with high phosphate metabolism(PM+)were significantly enriched in areas close to the tumor boundary.Conclusions There is significant spatial metabolic remodeling at the HCC tumor boundary,and the boundary enrichment charac-teristics of PM+cells suggest that the mechanical force environment at the tumor boundary may regulate the meta-bolic state of cancer cells.