Integrative multi-omics analysis reveals a novel subtype of hepatocellular carcinoma with biological and clinical relevance.

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous tumor, and the development of accurate predictive models for prognosis and drug sensitivity remains challenging.

Methods: We integrated laboratory data and public cohorts to conduct a multi-omics analysis of HCC, which included bulk RNA sequencing, proteomic analysis, single-cell RNA sequencing (scRNA-seq), spatial transcriptomics sequencing (ST-seq), and genome sequencing. We constructed a tumor purity (TP) and tumor microenvironment (TME) prognostic risk model.

Up-regulated ITGB4 promotes hepatocellular carcinoma metastasis by activating hypoxia-mediated glycolysis and cancer-associated fibroblasts.

The pre-metastatic niche constructed by cancer-associated fibroblasts (CAFs) plays a key role in the hypoxic tumor microenvironment (TME), promoting hepatocellular carcinoma (HCC) metastasis. Integrin, which is involved in cell-to-cell or cell-to-matrix interactions and TME regulation, affects tumor metastasis. However, the complex interactions between integrin-mediated HCC cells and CAFs remain unclear.