ArticleFrontiers in oncology2021
Identification of Mutator-Derived Alternative Splicing Signatures of Genomic Instability for Improving the Clinical Outcome of Cholangiocarcinoma.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 6 citations in OpenAlex.
- Aberrant ALPP Expression Serves as a Prognostic Biomarker and Facilitates Cholangiocarcinoma Progression through Immune Evasion and PI3K-Akt Signaling Activation.International journal of medical sciences · 2025Article
- Novel Insights into PGM2L1 as a Prognostic Biomarker in Cholangiocarcinoma: Implications for Metabolic Reprogramming and Tumor Microenvironment Modulation.International journal of medical sciences · 2025Article
- Identifying Strong Neoantigen MHC-I/II Binding Candidates for Targeted Immunotherapy with SINE.International journal of molecular sciences · 2024Article
- Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors.Frontiers in oncology · 2023Article
- DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives.Cells · 2022Review
- Characterization of the Estrogen Response Helps to Predict Prognosis and Identify Potential Therapeutic Targets in Cholangiocarcinoma.Frontiers in oncology · 2022Article
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7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCholangiocarcinoma is an aggressive carcinoma with increasing incidence and poor outcomes worldwide. Genomic instability and alternative splicing (AS) events are hallmarks of carcinoma development and progression. The relationship between genomic instability, AS events, and tumor immune microenvironment remain unclear.
methodsThe splicing profiles of patients with cholangiocarcinoma were obtained from The Cancer Genome Atlas (TCGA) spliceSeq database. The transcriptomics, simple nucleotide variation (SNP) and clinical data of patients with cholangiocarcinoma were obtained from TCGA database. Patients were divided into genomic unstable (GU-like) and genomic stable (GS-like) groups according to their somatic mutations. Survival-related differential AS events were identified through integrated analysis of splicing profiling and clinical data. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was used to identify AS events occurring in genes enriched in cancer pathways. Pearson correlation was applied to analyze the splicing factors regulating AS events. CIBERSORT was used identify differentially infiltrating immune cells.
resultsA prognostic signature was constructed with six AS events. Using this signature, the hazard ratio of risk score for overall survival is 2.362. For TCGA patients with cholangiocarcinoma, the area under the receiver operating characteristic curve is 0.981. CDK11A is a negative regulator of survival associated AS events. Additionally, the CD8+ T cell proportion and PD-L1 expression are upregulated in patients with cholangiocarcinoma and high splicing signatures.
conclusionWe provide a prognostic signature for cholangiocarcinoma overall survival. The CDK11A splicing factor and SLC46A1-39899-ES and IARS-86836-ES AS events may be potential targets for cholangiocarcinoma therapy. Patients with high AS risk score may be more sensitive to anti-PD-L1/PD1 immunotherapy.
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