Genome-Wide Profiling of Prognostic Alternative Splicing Signature in Colorectal Cancer

Abstract

Background: This study was to explore differential RNA splicing patterns and elucidate the function of the splice variants served as prognostic biomarkers in colorectal cancer (CRC).Methods: Genome-wide profiling of prognostic alternative splicing (AS) events using RNA-seq data from The Cancer Genome Atlas (TCGA) program was conducted to evaluate the roles of seven AS patterns in 330 colorectal cancer cohort. The prognostic predictors models were assessed by integrated Cox proportional hazards regression. Based on the correlations between survival associated AS events and splicing factors, splicing networks were built.Results: A total of 2,158 survival associated AS events in CRC were identified. Interestingly, most of these top 20 survival associated AS events were adverse prognostic factors. The prognostic models were built by each type of splicing patterns, performing well for risk stratification in CRC patients. The area under curve (AUC) of receiver operating characteristic (ROC) for the combined prognostic predictors model could reach 0.963. Splicing network also suggested distinguished correlation between the expression of splicing factors and AS events in CRC patients.Conclusion: The ideal prognostic predictors model for risk stratification in CRC patients was constructed by differential splicing patterns of 13 genes. Our findings enriched knowledge about differential RNA splicing patterns and the regulation of splicing, providing generous biomarker candidates and potential targets for the treatment of CRC.

Genome-Wide Profiling and Clinical Significance of Alternative Splicing Events in Glioblastoma

“…The present AS related genome-wide analysis identi ed seven AS modes in GBM patients, and showed that one gene was generally associated with two AS events, which is consistent with data in other tumors [26,27]. ES events accounted for approximately 50% of all AS events, indicating that they may be the most important AS events contributing to the malignancy of GBM; however, further functional experiments are necessary to con rm these ndings.…”

“…Considering stable traits and the applicability of risk signatures [26][27][28]31], we developed seven prognostic signatures based on the top three survival-related AS events. The results showed that all the AS-related signatures could signi cantly distinguish the survival status and serve as independent indicators of unfavorable prognosis.…”

Alternative Splicing Events as Indicators for the Prognosis of Uveal Melanoma

“…It is well known that alternative splicing (AS) is an important mechanism of post-transcriptional regulation that enables a single gene to produce multiple proteins, and nearly all human protein-coding genes will undergo alternative splicing [8]. Growing evidence has revealed that abnormal splicing events are closely related to carcinogenic processes including angiogenesis, apoptosis, proliferation, metastasis, and therapeutic drug resistance [9]. Thus, many cancer investigators are aware of the significance of AS and believe that it can take a potential role in therapeutic target.…”

Putatively cancer-specific alternative splicing is shared across patients and present in developmental and other non-cancer cells

“…Previous studies have established the importance of alternative and aberrant splicing in cancer prognosis (Bjørklund et al, 2017;Li et al, 2017;Marcelino Meliso et al, 2017;Robertson et al, 2018;Zhu et al, 2018;Zong et al, 2018) and have begun to explore its potential relevance in cancer immunotherapy (Kahles et al, 2018;Wood et al, 2019). In this study, we explore "novel" exon-exon junction use among cancers with respect to a broad collection of normal tissues and cells.…”