Genome-wide profiling of prognosis-related alternative splicing signatures in sarcoma

Abstract

Background: Sarcomas (SARCs) are rare malignant tumors with poor prognosis. Increasing evidence has suggested that aberrant alternative splicing (AS) is strongly associated with tumor initiation and progression.We considered whether survival-related AS events might serve as prognosis predictors and underlying targeted molecules in SARC treatment.Methods: RNA-Seq data of the SARC cohort were downloaded from The Cancer Genome Atlas (TCGA) database. Survival-related AS events were selected by univariate and multivariate Cox regression analyses.Metascape was used for constructing a gene interaction network and performing functional enrichment analysis. Then, prognosis predictors were established based on statistically significant survival-related AS events and evaluated by receiver operator characteristic (ROC) curve analysis. Finally, the potential regulatory network was analyzed via Pearson's correlation between survival-related AS events and splicing factors (SFs).Results: A total of 3,610 AS events and 2,291 genes were found to be prognosis-related in 261 SARC samples. The focal adhesion pathway was identified as the most critical molecular mechanism corresponding to poor prognosis. Notably, several prognosis predictors based on survival-related AS events showed excellent performance in prognosis prediction. The area under the curve of the ROC of the risk score was 0.85 in the integrated predictor. The splicing network proved complicated regulation between prognosis-related SFs and AS events. Also, driver gene mutations were significantly associated with AS in SARC patients.Conclusions: Survival-related AS events may become ideal indictors for the prognosis prediction of SARCs. Corresponding splicing regulatory mechanisms are worth further exploration.

Genome-Wide Profiling of Alternative Splicing Signatures Associated with Prognosis and Immune Microenvironment of Hepatocellular Carcinoma

“…Variation in AS signatures and cancer-specific AS events could be used as prognostic, predictive, and diagnostic biomarkers for different types of cancers. SpliceSeq analyses have been previously done to generate alterative splicing profiles for different cancers and to identify significant splicing events that can predict cancer prognosis [ 26 , 34 ]. Genome-wide analysis to generate AS profiles of HCC patients followed by identification of significant AS events to predict prognosis has also been done in several studies [ 15 – 18 ].…”

Comprehensive analysis of alternative splicing and transcriptome related to the prognosis of cervical squamous cell cancer

“…There is an increasing number of studies that AS plays a crucial role in the oncogenesis and development of cancer. Previous studies reported that AS may accurately evaluate prognostic outcomes in some cancers, including glioblastoma multiforme, colorectal cancer, prostate adenocarcinoma, bladder urothelial carcinoma, gastric cancer and so on [24][25][26]35]. However, the relevant research of cervical squamous cell cancer is scarce.…”

“…Therefore, it may be a credible prognostic biomarker and effective therapeutic target. Previous studies demonstrated that AS event-associated signatures may act as prognostic biomarkers in some cancers, including stomach adenocarcinoma, colorectal cancer, prostate adenocarcinoma, sarcoma, bladder urothelial carcinoma and so on [23][24][25][26][27]. However, comprehensive profiles of alternative splicing events are still scarce in cervical squamous cell cancer.…”

SEC23A Regulated by Splicing Factor EIF3A may be Involved in the Development of Cervical Squamous Cell Cancer via Adherens Junction Pathway

“…There is an increasing number of studies that AS plays a crucial role in the oncogenesis and development of cancer. Previous studies reported that AS may accurately evaluate prognostic outcomes in some cancers, including glioblastoma multiforme, colorectal cancer, prostate adenocarcinoma, bladder urothelial carcinoma, gastric cancer and so on [23,24]. However, the relevant research of cervical squamous cell cancer is scarce.…”

“…Previous studies demonstrated that AS event-associated signatures may act as prognostic biomarkers in some cancers, including stomach adenocarcinoma, colorectal cancer, prostate adenocarcinoma, sarcoma, bladder urothelial carcinoma and so on [21][22][23][24][25]. However, comprehensive pro les of alternative splicing events are still scarce in cervical squamous cell cancer.…”