Identification of an alternative splicing signature as an independent factor in colon cancer
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RESEARCH ARTICLE
Open Access
Identification of an alternative splicing signature as an independent factor in colon cancer Haitao Chen1, Jun Luo2,3 and Jianchun Guo2,3*
Abstract Background: Colon cancer is a common malignant tumor with a poor prognosis. Abnormal alternative splicing (AS) events played a part in the occurrence and metastasis of the tumor. We aimed to develop a survival-associated AS signature in colon cancer. Methods: The Percent Spliced In values of AS events were available in The Cancer Genome Atlas (TCGA) SpliceSeq database. Univariate Cox analysis was carried out to detect the prognosis-related AS events. We created a predictive model on account of the survival-associated AS events, which was further validated with a training-testing group design. Kaplan-Meier analysis was applied to assess patient survival. The area under curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive values of this model. Meanwhile, the clinical relevance of the signature and its regulatory relationship with splicing factors (SFs) were also evaluated. Results: In total, 2132 survival-related AS events were identified from colon cancer samples. We developed an elevenAS signature, in which the 5-year AUC value was 0.911. Meanwhile, the AUC values at five years were 0.782 and 0.855 in the testing and entire cohort, respectively. Multivariate Cox regression displayed that the T category and the risk score of the signature were independent risk factors of colon cancer survival. Also, we constructed an SFs-AS network based on 11 SFs and 48 AS events. Conclusions: We identified an eleven-AS signature of colon cancer. This signature could be treated as an independent prognostic factor. Keywords: Alternative splicing, Signature, Prognosis, Colon cancer
Background Colon cancer is one of the most common malignancies with a high death rate [1–3]. Despite significant development in tumor screening and treatment, the overall survival (OS) rates are still low in advanced patients [4–6]. Also, the prognosis may considerably differ in colon cancer patients with similar clinical characteristics due to * Correspondence: [email protected] 2 Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China 3 Wuhan University Center for Pathology and Molecular Diagnostics, Wuhan 430071, China Full list of author information is available at the end of the article
the high heterogeneity [7]. Hence, unraveling the mechanism of tumor development and further uncovering novel prognostic biomarkers for prediction and therapeutic assessment is urgently required. In the past few decades, major advance has been achieved in the highthroughput technologies for colon cancer, including gene microarray, total RNA-sequence, and whole genome bisulfite sequencing [8–13]. However, these results mostly focused on the change of gene expression levels, but ignored the diversity of RNA types regulated by alternative splicing (AS).
© The Author(s). 2020 Open Access This article is licensed under a Cr
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