Comparison Of Immune Profiles Between Cholangiocarcinoma And Hepatatocellular Carcinoma Subtypes

Liver cancer,due to its increasing incidence rate,mortality rated and limited treatment option,is becoming a global challenge to public health.Hepatocellular carcinoma(HCC)and cholangiocarcinoma(CCA)are two of the most common types of liver cancer,differed in epidemiology,risk factors and prognosis.HCC samples have molecular subtypes as well.Early-stage patients suffer from high recurrence rate after treatment and for advanced-stage patients,treatment could only provide improvement to survival time.Immunotherapy,especially immune checkpoint inhibitors,is becoming a promising treatment for several cancer types,including HCC.However,the response rate remains limited probably due to the heterogeneity of cancer.Difference in immune profiles may contribute to the variance in clinical features,prognosis and response to immunotherapy.This study aims to identify subtype-specific immune characteristics for CCA and HCC subtypes that might contribute to the prognosis and potential of immunotherapy.The immune profiles consist of immune-related genes,cytolytic activity,immune pathways and tumor-infiltrating lymphocytes.CCA and HCC-c1 samples showed an overall higher activation level of immune-related genes and pathways and this pattern was consistent in independent validation sets.We associated the difference in immune profiles with the activation level of cancer hallmarks and genomic mutations.There was a negative correlation between most of the metabolism pathway and immune-related pathways in both CCA and HCC.In HCC,CTNNB1/WNT-signaling pathway mutation appears to be associated with the expression of immune genes as well.These results reveal the difference of immune profiles,possible reasons and influence,which may deepen our understanding of the two cancer types and provide clues to clinical application.