ArticleDiscover oncology2025
Deciphering hypoxia's role in hepatocellular carcinoma prognosis with single-cell approaches.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Sohlh2 inhibited the angiogenesis of hepatocellular carcinoma through the HIF-1α/VEGFA pathway.Translational oncology · 2026Article
- Metal-organic frameworks-mediated reactive oxygen species modulation in the tumor microenvironment of digestive system malignancies: latest advances.Frontiers in chemistry · 2026Review
- Immune checkpoint biology in hepatocellular carcinoma (Review).Oncology letters · 2025Review
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Authors and funding
3 authors.
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Abstract
backgroundHepatocellular carcinoma (HCC), a prevalent and highly lethal malignancy, is notorious for its aggressive nature and inherent tendency to metastasize, posing significant challenges in clinical management and prognosis. Hypoxia, a pivotal characteristic of the tumor microenvironment (TME) in hepatocellular HCC, is intimately linked to disease progression and unfavorable patient outcomes, underscoring its critical role in shaping the malignant behavior of this cancer.
methodsOur research leveraged single-cell RNA sequencing technology to dissect the heterogeneity of the HCC TME, focusing on hypoxia-related genes. To probe the effects of hypoxia on HCC invasion, we developed the Cell Hypoxia-Related Prognostic Feature (CHPF). We analyzed transcriptome data from the The Cancer Genome Atlas (TCGA) database and the GSE149614 dataset, employing computational methods such as UMAP, Weighted correlation network analysis (WGCNA), and CellChat to identify hypoxia cells, characterize cell subsets, and elucidate intercellular communications.
resultsOur analysis revealed significant heterogeneity in hypoxia cell populations within the HCC TME, with distinct expression patterns of hypoxia-related genes in neoplastic and immune cells. Our analysis revealed distinct hypoxia subpopulations within HCC, with significant overexpression of genes like MEG3, KLF6 and JUN in hypoxia cells. We identified a unique hypoxia subpopulation with high invasive potential and constructed a prognostic model based on H2-specific transcription factors including LRP10、MED8、NOL10、NOP58 and REXO4. The model demonstrated significant predictive value for lifespan of patients as verified in the TCGA dataset and an external validation group.
conclusionKey transcription factors like NOP58, MED8 play pivotal roles in hypoxia-induced HCC invasion and metastasis, and a predictive model based on these factors forecasts HCC survival. Our findings provide novel molecular markers and therapeutic targets for HCC, highlighting the importance of considering the hypoxia TME in diagnostic and treatment strategies.
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