Molecular and Genomic Characterization of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) arises against a backdrop of chronic liver injury and exhibits profound molecular heterogeneity. Genomic analyses have revealed recurrent mutations in TERT, TP53 and CTNNB1, alongside diverse structural variants and copy number alterations that drive malignant transformation. Transcriptomic profiling delineates discrete molecular subclasses defined by metabolic activity, immune infiltration and cell‐cycle regulation, while proteomic studies highlight dysregulated signalling networks, notably in Wnt/β-catenin and MAPK pathways. Integration of multi-omics datasets has uncovered links between specific genetic alterations, tumour microenvironment composition and clinical outcome, underpinning the development of prognostic biomarkers and rational combination therapies. Together, these advances are refining our capacity to stratify patients for precision approaches and to target key vulnerabilities across global HCC populations.

Research from Nature Portfolio

Recent studies have mapped how oncogenic mutations shape the immune landscape of HCC. In murine models driven by NrasG12D, activation of the MAPK pathway induces MEK-ERK1/2-dependent GM-CSF release, recruiting immunosuppressive monocytes and sustaining an inflammatory, T cell-excluded microenvironment; blockade of GM-CSF synergises with VEGF inhibition to suppress tumour growth. Complementary whole-genome surveys of human liver cancers have defined distinct mutational signatures associated with exposures such as alcohol and aflatoxin, revealing dynamic shifts in signature prevalence during progression. These analyses link specific base-substitution and indel patterns to mutagenic agents, transcriptional activity and chromosomal rearrangements, offering a refined chronology of mutational processes that drive HCC evolution.

Molecular and Genomic Characterization of Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in molecular and genomic characterization of hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour microenvironment: The cellular and molecular milieu surrounding cancer cells, including immune infiltrates, stromal cells and extracellular matrix components that influence tumour behaviour.

Mutational signature: A characteristic pattern of base substitutions or indels in cancer genomes reflecting specific mutagenic processes or exposures.

Copy number alteration (CNA): A genomic event in which segments of DNA are duplicated or deleted, affecting gene dosage and function.

Transcriptomic profiling: The comprehensive measurement of RNA expression levels across the genome, used to classify tumour subtypes and infer pathway activity.

References

1. Precision treatment in advanced hepatocellular carcinoma. Cancer Cell (2024).
2. Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma. Nature Communications (2024).
3. Mutational signatures reveal the dynamic interplay of risk factors and cellular processes during liver tumorigenesis. Nature Communications (2017).
4. Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas. Biomarker Research (2023).
5. Metabolism‐associated molecular classification of hepatocellular carcinoma. Molecular Oncology (2020).
6. Proteomics of adjacent-to-tumor samples uncovers clinically relevant biological events in hepatocellular carcinoma. National Science Review (2023).