ArticleHepatology communications2026
The alternative splicing landscape of hepatocellular carcinoma and its potential for HCC detection.
Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Crosstalk between alternative splicing and non-coding RNAs in hepatocellular carcinoma: from regulatory mechanism to therapeutic implications.Non-coding RNA research · 2026Review
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Authors and funding
4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPre-mRNA alternative splicing contributes to oncogenic gene expression in hepatocellular carcinoma (HCC), and some oncogenic isoforms escape the tumor into circulation. This study aimed to characterize the alternative splicing landscape of HCC and investigate its potential for early detection by identifying HCC-specific alternative splicing events (ASEs) in peripheral fluids.
methodsWe analyzed RNA-Seq data from 787 HCC tumor samples across 16 studies to identify commonly mis-spliced ASEs. ASEs were examined in relation to HCC etiology, progression, and functional domain changes. We then identified HCC-tumor-associated ASEs in samples isolated from various peripheral fluids, including circulating epithelial cells (CECs), tumor-educated platelets, serum, and plasma. Machine-learning models were trained to classify HCC versus non-HCC based on ASEs in CECs and plasma.
resultsWe identified 3416 ASEs commonly mis-spliced in HCC across studies (FDR p<0.05, |ΔPSI|>0.1). We made these ASEs widely available through a new web application, HCC-INSIGHT (INvestigation of Spliced Isoforms and Genes in Human Tissues). Ten ASEs in CECs distinguished HCC from non-HCC in an independent test cohort with a balanced accuracy of 74%, 66% sensitivity, and 81% specificity. When combined with alpha-fetoprotein (AFP), classification performance improved to a balanced accuracy of 78%, 66% sensitivity, and 90% specificity.
conclusionsThis study provides a comprehensive characterization of ASEs in HCC and highlights their potential as circulating biomarkers. Our findings support the utility of ASEs in CECs for HCC detection, particularly in combination with AFP, although additional studies are needed to validate these ASEs in an independent prospective cohort. Finally, we introduce HCC-INSIGHT as a resource for further research into HCC splicing alterations.
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