ArticleJournal of gastrointestinal oncology2026
Prognostic genes in hepatocellular carcinoma and their function: an analysis integrating high-throughput-based spatial transcriptomics and single-cell RNA-sequencing.
Article in Journal of gastrointestinal oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Identifying novel prognostic indicators for patients with hepatocellular carcinoma (HCC) is critical to improving patient outcomes. Mapping the spatial composition of HCC tumors remains challenging. Therefore, this study aimed to identify prognostic genes and assess their role in HCC by integrating spatial transcriptome sequencing (ST-seq) and single-cell RNA sequencing (scRNA-seq). Methods: HCC-related datasets, including The Cancer Genome Atlas (TCGA)-HCC, International Cancer Genome Consortium (ICGC)-HCC, GSE149614, and GSE203612, were examined in this study. Single-cell and spatial transcriptome analyses were first conducted and followed by cell communication analysis. Target cell types with differential proportions and higher enrichment were identified. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was implemented to select prognostic genes and construct a risk model. Subsequently, a nomogram incorporating independent prognostic factors was developed, and immune microenvironment and immunotherapy response were analyzed. Finally, pseudotime analysis was performed to determine the developmental trajectory of the target cell types. Results: Among hepatocytes, T/natural killer (NK) cells, B cells, myeloid cells, fibroblasts, and endothelial cells, hepatocytes and T/NK cells were identified as target cell types. ST analysis delineated seven cell subclusters (C0-C6). Cell communication analysis indicated that hepatocytes interact more strongly with other cell types compared to T/NK cells. The number of interactions between C4 and other cell subclusters was higher than the interaction intensity. Of the seven prognostic genes, Conclusions: This study identified hepatocytes, T/NK cells, and seven prognostic genes in HCC, constructed a risk model and nomogram capable of predicting patient prognosis, and revealed through computational prediction that patients in the high-risk group might exhibit a poor response to immunotherapy, thereby providing new potential tools for the clinical treatment of HCC.
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