The Association between Immune Subgroups and Gene Modules for the Clinical, Cellular, and Molecular Characteristic of Hepatocellular Carcinoma.

The heterogeneity of hepatocellular carcinoma (HCC) is related to immune cell infiltration and genetic aberrations in the tumor microenvironment. This study aimed to identify the novel molecular typing of HCC according to the genetic and immune characteristics, to obtain accurate clinical management of this disease. We performed consensus clustering to divide 424 patients into different immune subgroups and assessed the reproducibility and efficiency in two independent cohorts with 921 patients. The associations between molecular typing and molecular, cellular, and clinical characteristics were investigated by a multidimensional bioinformatics approach. Furthermore, we conducted graph structure learning-based dimensionality reduction to depict the immune landscape to reveal the interrelation between the immune and gene systems in molecular typing. We revealed and validated that HCC patients could be segregated into 5 immune subgroups (IS1-5) and 7 gene modules with significantly different molecular, cellular, and clinical characteristics. IS5 had the worst prognosis and lowest enrichment of immune characteristics and was considered the immune cold type. IS4 had the longest overall survival, high immune activity, and antitumorigenesis, which were defined as the immune hot and antitumorigenesis types. In addition, immune landscape analysis further revealed significant intraclass heterogeneity within each IS, and each IS represented distinct clinical, cellular, and molecular characteristics. Our study provided 5 immune subgroups with distinct clinical, cellular, and molecular characteristics of HCC and may have clinical implications for precise therapeutic strategies and facilitate the investigation of immune mechanisms in HCC.