Comprehensive Analysis of Alternative Splicing in Gastric Cancer Identifies Epithelial–Mesenchymal Transition Subtypes Associated with Survival
Autor: | Yukyung Jun, Yun-Suhk Suh, SungHee Park, Jieun Lee, Jong-Il Kim, Sanghyuk Lee, Wan-Ping Lee, Olga Anczuków, Han-Kwang Yang, Charles Lee |
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Rok vydání: | 2021 |
Předmět: |
Adult
Aged 80 and over Male Cancer Research Epithelial-Mesenchymal Transition Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling RNA-Binding Proteins Kaplan-Meier Estimate Middle Aged Gene Expression Regulation Neoplastic Alternative Splicing Oncology Stomach Neoplasms Cell Line Tumor Cluster Analysis Humans Female RNA Splicing Factors RNA-Seq Aged |
Zdroj: | Cancer Research. 82:543-555 |
ISSN: | 1538-7445 0008-5472 |
Popis: | Alternatively spliced RNA isoforms are a hallmark of tumors, but their nature, prevalence, and clinical implications in gastric cancer have not been comprehensively characterized. We systematically profiled the splicing landscape of 83 gastric tumors and matched normal mucosa, identifying and experimentally validating eight splicing events that can classify all gastric cancers into three subtypes: epithelial-splicing (EpiS), mesenchymal-splicing (MesS), and hybrid-splicing. These subtypes were associated with distinct molecular signatures and epithelial–mesenchymal transition markers. Subtype-specific splicing events were enriched in motifs for splicing factors RBM24 and ESRP1, which were upregulated in MesS and EpiS tumors, respectively. A simple classifier based only on RNA levels of RBM24 and ESRP1, which can be readily implemented in the clinic, was sufficient to distinguish gastric cancer subtypes and predict patient survival in multiple independent patient cohorts. Overall, this study provides insights into alternative splicing in gastric cancer and the potential clinical utility of splicing-based patient classification. Significance: This study presents a comprehensive analysis of alternative splicing in the context of patient classification, molecular mechanisms, and prognosis in gastric cancer. |
Databáze: | OpenAIRE |
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