Identification of the prognostic signature based on genomic instability-related alternative splicing in colorectal cancer and its regulatory network

• DOI: 10.3389/fbioe.2022.841034
• Publication Date: 2022-07-18T07:06:22Z
• Authors: Qiuying Ding; Zhengping Hou; Zhibo Zhao; Yao Chen; Lei Zhao; Yue Xiang
• Keywords: Identification; Signature (topology); Microsatellite Instability

Background: Colorectal cancer (CRC) is a heterogeneous disease with many somatic mutations defining its genomic instability. Alternative Splicing (AS) events, are essential for maintaining However, the role of instability-related AS events in CRC has not been investigated. Methods: From The Cancer Genome Atlas (TCGA) program, we obtained splicing profiles, single nucleotide polymorphism, transcriptomics, and clinical information CRC. Combining mutation data, signature was constructed Mutations analyses, stratification multivariate Cox regression analyses evaluated this training set. Subsequently, validated sensitivity specificity prognostic using test set entire TCGA dataset. We nomogram prognosis prediction patients. Differentially infiltrating immune cells were screened by CIBERSORT. Inmmunophenoscore (IPS) analysis used to evaluate response immunotherapy. events-related factors (SF) analyzed Pearson’s correlation. effects SF regulating proliferation migration Caco2 cells. Results: A consisting seven (PDHA1-88633-ES, KIAA1522-1632-AP, TATDN1-85088-ES, PRMT1-51042-ES, VEZT-23786-ES, AIG1-77972-AT, PHF11-25891-AP) constructed. Patients high-risk score group showed higher mutation. instability risk an independent variable associated overall survival (OS), hazard ratio 1.537. area under curve receiver operator characteristic predicting OS patients 0.733. Furthermore, established could be clinically stratify predict prognosis. defined as lower proportion eosinophils than low-risk group. low more sensitive anti-CTLA4 Additionally, HSPA1A FAM50B two OS-related AS. Downregulation inhibited Conclusion: ideal reflecting verified important