Abstract
BackgroundColon adenocarcinoma (COAD) is one of the most common malignant tumors, with high incidence and mortality rates worldwide. Reliable prognostic biomarkers are needed to guide clinical practice.MethodsComprehensive gene expression with alternative splicing (AS) profiles for each patient was downloaded using the SpliceSeq database from The Cancer Genome Atlas. Cox regression analysis was conducted to screen for prognostic AS events. The R package limma was used to screen differentially expressed genes (DEGs) between normal and tumor samples in the COAD cohort. A Venn plot analysis was performed between DEGs and prognostic AS events, and the DEGs that co-occurred with prognostic AS events (DEGAS) were identified. The top 30 most-connected DEGAS in protein–protein interaction analysis were identified through Cox proportional hazards regression to establish prognostic models.ResultsIn total, 350 patients were included in the study. A total of 22,451 AS events were detected, of which 2004 from 1439 genes were significantly associated with survival time. By overlapping these 1439 genes with 6455 DEGs, 211 DEGs with AS events were identified. After the construction of the protein–protein interaction network, the top 30 hub genes were included in a multivariate analysis. Finally, a risk score based on 12 genes associated with overall survival was established (P < 0.05). The area under the curve was 0.782. The risk score was an independent predictor (P < 0.001).ConclusionsBy exploring survival-associated AS events, a powerful prognostic predictor consisting of 12 DEGAS was built. This study aims to propose a novel method to provide treatment targets for COAD and guide clinical practice in the future.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the third most common cause of tumor-related death
Overview of alternative splicing (AS) events in Colon adenocarcinoma (COAD) Comprehensive AS events were identified in seven splicing types: exon skip (ES), mutually exclusive exon (ME), retained intron (RI), alternate promoter (AP), alternate terminator (AT), alternate donor site (AD), and alternate acceptor site (AA) (Fig. 1a)
AS events associated with survival time The results of univariate Cox regression analysis showed that 2004 AS events in 1439 genes were significantly associated with overall survival (OS) (P < 0.05), including 10
Summary
Colorectal cancer (CRC) is the third most common cancer and the third most common cause of tumor-related death. There is increasing evidence that the transcript variants of a gene may have opposing roles and that widespread splicing disorders are one of the molecular markers of tumorigenesis and participate in many oncogenic processes, including proliferation, invasion and metastasis, apoptosis, hypoxia, metabolism, angiogenesis, and immune escape [6, 7]. Various studies have shown that specific siRNAs, lncRNAs, and miRNAs affect the tumorigenesis and prognosis of COAD [10, 11]. Some gene modifications such as acetylation and N6-methyladenosine are research hotspots in the field of COAD [12, 13].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
