The Study About Clinicopathological Significance Of Vessels Encapsulating Tumor Clusters(VETC)Pattern In Hepatocellular Carcinoma And The Mechanism

Objective: To analyze the correlation between Vessels Encapsulate Tumor Clusters(VETC)and clinicopathological characteristics of hepatocellular carcinoma(HCC),and explore the molecular mechanism of VETC in HCC and its correlation with immune cell infiltration,to provide a basis for the discovery of targets for VETC immunotherapy drugs..Methods: In this study,we analyzed the correlation between the clinicopathological characteristics of HCC patients with VETC pattern,and the correlation between VETC and infiltration of CD4 positive or CD8 positive lymphocyte in liver cancer by immunohistochemistry;Multiple immunofluorescence staining was used to analyze the difference of infiltrated immune cells between HCC with VETC pattern and HCC with capillary(CAP)pattern;The different genes between HCC patients with VETC pattern and HCC patients with CAP pattern were screened by RNA sequencing,and cluster analysis,enrichment analysis of functions and pathways were performed to explore the formation mechanism and immune correlation of HCC patients with VETC type pattern;through single cell sequencing,all cells in VETC type HCC tissues and CAP type HCC tissues were sequenced and analyzed,after data comparison,quality control and standardization were completed,the cell clusters were identified according to differentially expressed marker genes,and the same subgroups were merged.The function and pathway enrichment analysis were performed on the differentially expressed genes of the interested cancer cell subgroups and immune cell subgroups.Results: VETC vascular pattern is positively correlated with AFP serum concentration,BCLC staging,tumor size,Edmondson grading microvascular invasion and trabecular type,negatively correlated with solid type in the pathological classification of HCC;Lymphocyte infiltration was significantly reduced in VETC pattern HCC tissues.VETC pattern was significantly correlated with PFS and OS in patients with HCC.AFP serum concentration and Ki67 index were independent factors affecting PFS,while AFP serum concentration,BCLC stage,and vascular pattern were independent risk factors affecting OS in patients with HCC.VETC pattern of HCC has special histopathological and imaging characteristics and is significantly related to the poor prognosis of patients;compared with HCC patients with CAP pattern,CD4 positive or CD8 positive lymphocytes were significantly decreased in HCC patients with VETC pattern,and VETC was significantly correlated with decreased infiltration of lymphocytes;in VETC pattern of HCC,the glucose metabolism and lipid metabolism of tumor cells were enhanced,CD4-positive naive T cells have decreased cell differentiation,signal transduction and immune function,but increased lipid metabolism.The above metabolic changes resulted in lipid accumulation in the tumor microenvironment,leading to decreased immune function of CD4-positive naive T cells.Conclusion: VETC pattern had special histopathological characteristics and was significantly correlated with PFS and OS in patients with HCC.VETC pattern was an independent risk factor affecting the prognosis of patients with hepatocellular carcinoma.Infiltration of lymphocytes decreased in HCC with VETC pattern;VETC pattern of HCC has increased glucose metabolism and lipid metabolism,decreased activation of immune cells,and overall immunosuppression.