HCC: RNA-Sequencing in Cirrhosis

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Hepatocellular carcinoma (HCC) is a leading cause of cancer death, often arising from chronic liver disease and cirrhosis.
• The precise molecular mechanisms driving HCC development from cirrhosis remain incompletely understood.
• Identifying molecular alterations is crucial for improving HCC prognosis.

Purpose of the Study:

• To investigate transcriptome-wide mRNA expression changes during HCC development from cirrhosis.
• To identify key molecular pathways, particularly fatty acid metabolism (FAM), involved in HCC progression.
• To develop and validate a prognostic signature for cirrhotic HCC patients.

Main Methods:

• RNA-sequencing was performed on cirrhosis, HCC, and adjacent non-tumor tissues.
• Bioinformatic analyses, including Mfuzz clustering and enrichment analysis, identified differentially expressed genes (DEGs) and pathways.
• A FAM-related prognostic signature was constructed using TCGA data and validated in independent cohorts.

Main Results:

• 2012 differentially expressed mRNAs were identified between tissue types.
• Fatty acid metabolism was highlighted as a critical pathway in HCC development.
• A FAM-based prognostic model and nomogram accurately predicted survival in cirrhotic HCC patients.
• The prognostic signature correlated with the tumor immune microenvironment.
• ADH1C was found to be downregulated in HCC, and its silencing promoted HCC cell proliferation and motility.

Conclusions:

• Transcriptome analysis reveals significant mRNA alterations and implicates fatty acid metabolism in cirrhotic HCC.
• A novel FAM-related prognostic signature offers predictive value for HCC patient outcomes and immune relevance.
• ADH1C represents a potential tumor suppressor in HCC, warranting further investigation.