Project description:The inter-patient variability of tumor proteomes has been investigated on a large scale but many tumors display also intra-tumoral heterogeneity (ITH) regarding morphological and genetic features. To what extent the local proteome of tumors intrinsically differs remains largely unknown. Here, we used hepatocellular carcinoma (HCC) as a model system, to quantify both inter- and intra-tumor heterogeneity across human patient specimens with spatial resolution. We first defined proteomic features that robustly distinguish neoplastic from the directly adjacent non-neoplastic tissue by integrating proteomic data from human patient samples and genetically defined mouse models with available gene expression data. We then demonstrated the existence of intra-tumoral variations in protein abundance that re-occur across different patient samples, and affect clinically relevant proteins, even in the absence of obvious morphological differences or genetic alterations. Our work demonstrates the suitability and the benefits of using mass spectrometry based proteomics to analyze diagnostic tumor specimens with spatial resolution
Project description:As immunotherapy plays an increasingly important role in the treatment of hepatocellular carcinoma, the immune infiltration heterogeneity of the tumor provides an important reference for immunotherapy decisions. In this study, a mouse hepatocellular carcinoma model was established, and the intra-tumor and peritumor tissues were sampled and analyzed by RNA sequencing, respectively, to explore the heterogeneity of immune-related gene expression in intra- and peritumor regions.
