PTM-Related Signatures Predict Lymph Node Metastasis and Shape Microenvironment in Hepatocellular Carcinoma: A...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) with lymph node metastasis (LNM) has a poor prognosis.
• The role of protein post-translational modifications (PTMs) in HCC LNM and tumor microenvironment (TME) dynamics remains unclear.

Purpose of the Study:

• To investigate the role of PTMs in HCC LNM.
• To identify prognostic genes and develop a risk model for HCC patients with LNM.
• To explore the association between identified genes, TME, and genomic alterations.

Main Methods:

• Systematic analysis of single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data.
• Identification of differentially expressed genes (DEGs) and PTM-related candidate genes.
• Cox regression and random survival forest (RSF) model for prognostic gene identification and risk stratification.
• Analysis of TME features, genomic alterations, immune checkpoints, and drug sensitivity.

Main Results:

• Hepatocyte populations were expanded in both LNM and non-LNM HCC groups.
• PJA1 and RFPL4B were identified as prognostic risk factors and integrated into an RSF model.
• High-risk patients showed poor survival, increased tumor mutational burden, and altered TME.
• LNM-associated hepatocytes displayed arrested differentiation and dysregulated transcription factor activity.

Conclusions:

• PJA1 and RFPL4B are novel PTM-related prognostic genes associated with HCC LNM.
• The developed risk model effectively stratifies patients based on TME and genomic instability.
• Hepatocyte differentiation arrest and transcription factor network dysregulation may drive metastatic progression in HCC.