Objective: This research aimed to identify alternative splicing (AS) variants in hepatocellular carcinoma (HCC) and assess their prognostic biomarker potential. We analyzed genome-wide prognostic-associated AS events to pinpoint specific genes that could predict HCC patient outcomes and serve as therapeutic targets.
Methods: Analyzing 343 liver cancer samples from The Cancer Genome Atlas (TCGA) via RNA-seq, we evaluated the impact of seven AS patterns on HCC. We constructed a prognostic prediction model using Cox proportional hazards regression and developed a splicing network by correlating survival-associated AS events with splicing factor expression. Notably, we investigated Formiminotransferase cyclodeaminase (FTCD) gene for its role in liver cancer cell proliferation and pathway mechanisms in mice and cell models.
Results: We discovered 3164 survival-associated AS events, with the top 20 mostly indicating poor prognosis. Our prognostic model, integrating various AS patterns, demonstrated robust performance in stratifying HCC risk (AUC = 0.830). Splicing network analysis highlighted significant correlations between splicing factors and AS events. Lower expression of FTCD, associated with adverse HCC outcomes, was found to regulate cell proliferation via the PI3K/AKT/mTOR pathway.
Conclusion: This study offers a prognostic prediction model for HCC patient risk stratification, identifying the FTCD gene as a crucial prognostic marker and therapeutic target. This highlights FTCD's potential impact on HCC clinical diagnosis and treatment strategies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599552 | PMC |
| http://dx.doi.org/10.1007/s12672-024-01201-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.
Nat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
View Article and Find Full Text PDFEffects of acute PM purification on cognitive function and underlying mechanisms: Evidence from integrating alternative splicing into multi-omics.
J Hazard Mater
January 2025
Vanke School of Public Health, Tsinghua University, Beijing 100084, China; Institute for Healthy China, Tsinghua University, Beijing 100084, China. Electronic address:
The relationship between fine particulate matter (PM) and cognition has been extensively investigated. However, the causal impact of acute PM purification on cognition improvement and the underlying biological mechanisms remain relatively opaque. Our double-blinded randomized controlled trial assessed the impact of acute PM purification on executive function, underpinned by multi-omics approaches including alternative splicing (AS) analysis.
View Article and Find Full Text PDFAberrant acetylation caused by a CDYL splicing mutation contributes to thin mid-piece related asthenoteratozoospermia and male infertility.
Andrology
January 2025
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Objectives: Acetylated tubulin is a hallmark of flagellar stability in spermatozoa, and studies have demonstrated the ability of CDYL to function as a tubulin acetyltransferase in spermatozoa. Of note, germline conditional knockout of Cdyl can lead to asthenoteratozoospermia and infertility in male mice. However, the role of CDYL gene in human fertility remains uncharacterized.
View Article and Find Full Text PDFImpact of rare non-coding variants on human diseases through alternative polyadenylation outliers.
Nat Commun
January 2025
Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen, China.
Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), including 1334 3' UTR and 200 intronic aOutliers, from 15,201 samples across 49 human tissues. These aOutliers exhibit unique characteristics from transcription or splicing outliers, with a pronounced RV enrichment.
View Article and Find Full Text PDFCoordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex.
Cell Rep
January 2025
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Chromatin regulatory proteins are expressed broadly and assumed to exert the same intrinsic function across cell types. Here, we report that 14 chromatin regulators undergo evolutionary-conserved neuron-specific splicing events involving microexons. Among them are two components of a histone demethylase complex: LSD1 H3K4 demethylase and the H3K4me0-reader PHF21A.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!