Decoding Liver Cancer Prognosis: from Multi-omics Subtypes, Prognostic Models to Single Cell Validation

Purpose: Hepatocellular carcinoma (HCC) is a highly aggressive tumor characterized by significant heterogeneity and invasiveness, leading to a lack of precise individualized treatment strategies and poor patient outcomes. This necessitates the urgent development of accurate patient stratification methods and targeted therapies based on distinct tumor characteristics. Experimental Design: By integrating gene expression data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO), we identified subtypes through a multi-omics consensus clustering approach amalgamated from 10 clustering techniques. Subsequently, we developed a prognostic model, employing machine learning algorithms, based on subtype classification features. Finally, by analyzing single cell sequencing data, we investigated the mechanisms driving prognostic variations among distinct subtypes. Results: First, we developed a novel consensus clustering method that categorizes liver cancer patients into two subtypes, CS1 and CS2. Second, we constructed a prognostic prediction model, which demonstrated superior predictive accuracy compared to several models published in the past five years. Finally, we observed differences between CS1 and CS2 in various metabolic pathways, biological processes, and signaling pathways, such as fatty acid metabolism, hypoxia levels, and the PI3K-AKT signaling pathway. ### Competing Interest Statement The authors have declared no competing interest.