ArticleMolecular medicine (Cambridge, Mass.)2021
Identification of prognostic alternative splicing events related to the immune microenvironment of hepatocellular carcinoma.
Article in Molecular medicine (Cambridge, Mass.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 15 citations in OpenAlex.
- Crosstalk between alternative splicing and non-coding RNAs in hepatocellular carcinoma: from regulatory mechanism to therapeutic implications.Non-coding RNA research · 2026Review
- The alternative splicing landscape of hepatocellular carcinoma and its potential for HCC detection.Hepatology communications · 2026Article
- Modulation of the PD-1/PD-L1 axis and tumor immunity by metals and metalloids: mechanistic insights and human health implications.Frontiers in immunology · 2026Review
- Systematic exploration of prognostic alternative splicing events related to tumor immune microenvironment of Clear Cell Renal Cell Carcinoma.Cancer biomarkers : section A of Disease markers · 2025Article
- Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway.iScience · 2025Article
- Alternative splicing of IRF3 plays an important role in the development of hepatocarcinoma.Epigenetics · 2023Article
- Construction of a novel signature based on immune-related lncRNA to identify high and low risk pancreatic adenocarcinoma patients.BMC gastroenterology · 2023Article
- Key Genes Associated with Tumor-Infiltrating Non-regulatory CD4- and CD8-Positive T Cells in Microenvironment of Hepatocellular Carcinoma.Biochemical genetics · 2022Article
- Comprehensive characterization of 11 prognostic alternative splicing events in ovarian cancer interacted with the immune microenvironment.Scientific reports · 2022Article
- N6-methyladenosine RNA methylation regulator-related alternative splicing gene signature as prognostic predictor and in immune microenvironment characterization of patients with low-grade glioma.Frontiers in genetics · 2022Article
- Identification of Prognostic lncRNA Related to the Immune Microenvironment of Soft Tissue Sarcoma.BioMed research international · 2022Article
- Sempervirine Inhibits Proliferation and Promotes Apoptosis by Regulating Wnt/β-Catenin Pathway in Human Hepatocellular Carcinoma.Frontiers in pharmacology · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its 5-year survival rate is less than 20%, despite various treatments being available. Increasing evidence indicates that alternative splicing (AS) plays a nonnegligible role in the formation and development of the tumor microenvironment (TME). However, the comprehensive analysis of the impact on prognostic AS events on immune-related perspectives in HCC is lacking but urgently needed.
methodsThe transcriptional data and clinical information of HCC patients were downloaded from TCGA (The Cancer Genome Atlas) database for calculating immune and stromal scores by ESTIMATE algorithm. We then divided patients into high/low score groups and explored their prognostic significance using Kaplan-Meier curves. Based on stromal and immune scores, differentially expressed AS events (DEASs) were screened and evaluated with functional enrichment analysis. Additionally, a risk score model was established by applying univariate and multivariate Cox regression analyses. Finally, gene set variation analysis (GSVA) was adopted to explore differences in biological behaviors between the high- and low-risk subgroups.
resultsA total of 370 HCC patients with complete and qualified corresponding data were included in the subsequent analysis. According to the results of ESTIMATE analysis, we observed that the high immune/stromal score group had a longer survival probability, which was significantly correlated with prognosis in HCC patients. In addition, 467 stromal/immune score-related DEASs were identified, and enrichment analysis revealed that DEASs were significantly enriched in pathways related to HCC tumorigenesis and the immune microenvironment. More importantly, the final prognostic signature containing 16 DEASs showed powerful predictive ability. Finally, GSVA demonstrated that activation of carcinogenic pathways and immune-related pathways in the high-risk group may lead to poor prognosis.
conclusionsCollectively, these outcomes revealed prognostic AS events related to carcinogenesis and the immune microenvironment, which may yield new directions for HCC immunotherapy.
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