Genomic and immune landscape in hepatocellular carcinoma: Implications for personalized therapeutics.
Jiaoyun ZhengJunyan ChenShuchao WangDun YangPeng ZhouPublished in: Environmental toxicology (2023)
Hepatocellular carcinoma (HCC) is a globally prevalent malignancy, marked by genetic heterogeneity and intricate tumor microenvironment interactions. In this study, we undertook a detailed single-cell analysis of six active HCC patients, highlighting strong correlations between gene expression levels and cellular characteristics. UMAP clustering revealed seven distinct cell categories with associated gene expressions. A divergence was observed in tumor cells into high and low cuproptosis groups, each associated with distinct pathways: oxidative stress for the high cuproptosis group and inflammatory and angiogenesis pathways for the low group. CellChat analysis on the TCGA-LIHC cohort displayed unique intercellular interactions among hepatocytes, T cells, and other cells, with pathways like COLLAGEN and VEGF being pivotal. Functional enrichment analyses exposed pathways enriched between cuproptosis groups, with KEGG emphasizing diseases like Parkinson's. COX survival analysis identified key prognostic genes, revealing distinct survival rates between risk groups in TCGA and GSE14520 cohorts. Mutation data highlighted missense mutations, with TTN, TP53, and CTNNB1 being the most mutated in HCC. Immune infiltration analysis via CIBERSORTx indicated differences between risk groups in NK cells, neutrophils, and other cells. Our drug sensitivity investigation showed significant correlations between model genes and drug responsiveness, emphasizing the importance of patient risk stratification for therapeutic approaches. Further, ATP6V1G1 was recognized in its role in apoptosis and migration in HCC cells. In conclusion, our findings illuminate the complexities of HCC progression, potential predictive genetic markers for drug response, and the pivotal role of ATP6V1G1, suggesting avenues for targeted therapeutic strategies in HCC.
Keyphrases
- single cell
- induced apoptosis
- cell cycle arrest
- oxidative stress
- genome wide
- gene expression
- endoplasmic reticulum stress
- rna seq
- copy number
- cell death
- dna methylation
- high throughput
- newly diagnosed
- endothelial cells
- small molecule
- emergency department
- stem cells
- signaling pathway
- pi k akt
- cell therapy
- dna damage
- prognostic factors
- drug induced
- vascular endothelial growth factor
- drug delivery
- intellectual disability
- risk assessment
- end stage renal disease
- machine learning
- liver injury
- transcription factor
- deep learning
- case report
- bone marrow
- ischemia reperfusion injury
- diabetic rats
- human health