Single-cell transcriptome analysis reveals PDCD10's role in immune regulation and its correlation with oxidative stress in hepatocellular carcinoma.
Abstract Background: Hepatocellular carcinoma (HCC) is a highly malignant cancer with a poor prognosis. Its progression is significantly influenced by cellular heterogeneity, which complicates the understanding of its molecular mechanisms and contributes to the challenges in developing effective treatments. Methods: We conducted an extensive analysis of single-cell RNA sequencing (scRNA-seq) data to identify distinct subpopulations within HCC, integrating these findings with clinical and prognostic data from The Cancer Genome Atlas (TCGA). Our bioinformatics workflow encompassed gene set enrichment analysis (GSEA), immune cell infiltration assessment, evaluation of immunotherapy-related factors, pseudotime trajectory inference, cell–cell communication profiling, and mutation analysis. To further investigate the functional relevance of the identified molecular features, we validated this finding using immunofluorescence analysis and Western blotting (WB). Results: This study identified molecular features associated with oxidative stress in the myeloid subpopulation as potential prognostic biomarkers and therapeutic targets for HCC. scRNA-seq revealed significant correlations between ADAM9, ECT2, ATP13A2, and PDCD10 expression and patient prognosis, highlighting their roles in HCC progression. Notably, PDCD10 emerged as a key factor driving epithelial-mesenchymal transition (EMT) and immune regulation. Its high expression is strongly associated with immune checkpoint regulation and key oncogenic mutations, such as TP53 and CTNNB1. Further experiments have shown that PDCD10 overexpression may contribute to the antioxidant stress response and immune regulation in cancer. These findings provide new mechanistic insights and position PDCD10 as a promising therapeutic target. Conclusion: This study identified oxidative stress-related molecular features in the myeloid subpopulation as potential prognostic biomarkers and available targets for immunotherapy, providing insights into the progression of HCC.
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Ma et al. (2025) studied this question.
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