scholarly journals Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases

2018 ◽  
Vol 48 (3) ◽  
pp. 1355-1368 ◽  
Author(s):  
Rong-quan He ◽  
Xian-guo Zhou ◽  
Qiao-yong Yi ◽  
Cai-wang Deng ◽  
Jia-min Gao ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Urothelial Carcinoma ◽  
Risk Score ◽  
Regulatory Network ◽  
Pearson Correlation ◽  
Risk Scores ◽  
Pathway Enrichment Analysis ◽  
Splicing Factors ◽  
Bladder Urothelial Carcinoma ◽  
Alternative Splicing Events

Background/Aims: Increasing evidences indicated the important roles of alternative splicing in the progression and prognosis of bladder urothelial carcinoma (BLCA). However, most previous research has focused on one or several alternative splicing events, without a comprehensive evaluation of the prognostic value of splicing events in BLCA. In this study, we aimed to determine risk scores for predicting prognosis of BLCA patients based on splicing events. Methods: RNA-sequencing data and clinical information of BLCA patients were downloaded from The Cancer Genome Atlas, and data of splicing events were obtained from the SpliceSeq database. Univariate and multivariate Cox regression analyses were employed to identify survival-associated alternative spicing events (SASEs) and to calculate risk scores. Protein-protein interaction analysis of genes of the SASEs was performed using STRING, a database of known and predicted protein-protein interactions, and pathway enrichment analysis of the genes was implemented using the Database for Annotation, Visualization and Integrated Discovery (version 6.8). Receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to evaluate the clinical significance of genes from the SASEs for building a risk score in BLCA. Correlation between splicing events of splicing factors and non-splicing factors were analyzed with Pearson correlation coefficient. A potential regulatory network was then built using Cytoscape 3.5. Results: In total, 39,508 alternative splicing events in 317 patients with BLCA were analyzed, including 4,632 SASEs. The area under the curve of the ROC of risk score (all) was 0.748 for predicting survival status of BLCA patients. Low- and high-risk score groups classified using the median “risk score (all)” value displayed remarkably different survival time (Low vs. High = 3304.841±239.758 vs 1198.614±152.460 days). The potential regulatory network with SASEs of splicing factors and other genes was constructed, which might be part of the biological mechanisms associated with prognosis of BLCA patients. Conclusions: In this study, prognostic signatures constructed using splicing events could be used for predicting the prognosis of BLCA patients.

scholarly journals Whole Genome Analysis and Prognostic Model Construction Based on Alternative Splicing Events in Endometrial Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Caixia Wang ◽  
Mingjun Zheng ◽  
Shuang Wang ◽  
Xin Nie ◽  
Qian Guo ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Alternative Splicing ◽  
Risk Score ◽  
Genome Analysis ◽  
Prognostic Model ◽  
Cox Regression ◽  
Splicing Factors ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Alternative Splicing Events

Objectives. A growing body of evidence has shown that aberrant alternative splicing (AS) is closely related to the occurrence and development of cancer. However, prior studies mainly have concentrated on a few genes that exhibit aberrant AS. This study aimed to determine AS events through whole genome analysis and construct a prognostic model of endometrial cancer (EC). Methods. We downloaded gene expression RNAseq data from UCSC Xena, and seven types of AS events from TCGA SpliceSeq. Univariate Cox regression was employed to analyze the prognostic-related alternative splicing events (PASEs) and splicing factors; multivariate Cox regression was conducted to analyze the effect of risk score (All) and clinicopathological parameters on EC prognosis. An underlying interaction network of PASEs of EC was constructed by Cytoscape Reactome FI, GO, and KEGG pathway enrichment was performed by DAVID. ROC curves and Kaplan-Meir analysis were used to assess the diagnostic value of prognostic model. The correlation between PASEs and splicing factors was analyzed by GraphPad Prism; then a network was constructed using Cytoscape. Results. In total, 28,281 AS events in EC were identified, which consisted of 1166 PASEs. RNPS1, NEK2, and CTNNB1 were the hub genes in the network of the top 600 PASEs. The area under the curve (AUC) of risk score (All) reached 0.819. Risk score (All) together with FIGO stage, cancer status, and primary therapy outcome success was risk factors of the prognosis of EC patients. Splicing factors YBX1, HNRNPDL, and HNRNPA1 were significantly related to the overall survival (OS). The splicing network indicated that the expression of splicing factors was significantly correlated with percent-splice-in (PSI) value of PASEs. Conclusion. We constructed a model for predicting the prognosis of EC patients based on PASEs using whole genome analysis of AS events and thereby provided a reliable theoretical basis for EC clinical prognosis evaluation.

scholarly journals Characterization of alternative splicing events and prognostic signatures in breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pihua Han ◽  
Jingjun Zhu ◽  
Guang Feng ◽  
Zizhang Wang ◽  
Yanni Ding
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Proportional Hazards ◽  
Pearson Correlation ◽  
Original Data ◽  
Cox Proportional Hazards ◽  
Prognostic Indicators ◽  
Splicing Factors ◽  
Rna Seq

Abstract Background Breast cancer (BRCA) is one of the most common cancers worldwide. Abnormal alternative splicing (AS) frequently observed in cancers. This study aims to demonstrate AS events and signatures that might serve as prognostic indicators for BRCA. Methods Original data for all seven types of splice events were obtained from TCGA SpliceSeq database. RNA-seq and clinical data of BRCA cohorts were downloaded from TCGA database. Survival-associated AS events in BRCA were analyzed by univariate COX proportional hazards regression model. Prognostic signatures were constructed for prognosis prediction in patients with BRCA based on survival-associated AS events. Pearson correlation analysis was performed to measure the correlation between the expression of splicing factors (SFs) and the percent spliced in (PSI) values of AS events. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to demonstrate pathways in which survival-associated AS event is enriched. Results A total of 45,421 AS events in 21,232 genes were identified. Among them, 1121 AS events in 931 genes significantly correlated with survival for BRCA. The established AS prognostic signatures of seven types could accurately predict BRCA prognosis. The comprehensive AS signature could serve as independent prognostic factor for BRCA. A SF-AS regulatory network was therefore established based on the correlation between the expression levels of SFs and PSI values of AS events. Conclusions This study revealed survival-associated AS events and signatures that may help predict the survival outcomes of patients with BRCA. Additionally, the constructed SF-AS networks in BRCA can reveal the underlying regulatory mechanisms in BRCA.

scholarly journals Genome-Wide Analyses of Prognostic and Therapeutic Alternative Splicing Signatures in Bladder Urothelial Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhongru Fan ◽  
Zhe Zhang ◽  
Chiyuan Piao ◽  
Zhuona Liu ◽  
Zeshu Wang ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Alternative Splicing ◽  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Gap Analysis ◽  
Unsupervised Cluster ◽  
Chemotherapy Drugs ◽  
Genome Wide ◽  
Bladder Urothelial Carcinoma ◽  
Unsupervised Cluster Analysis

BackgroundAlternative splicing (AS) is an indispensable post-transcriptional modification applied during the maturation of mRNA, and AS defects have been associated with many cancers. This study was designed to thoroughly analyze AS events in bladder urothelial carcinoma (BLCA) at the genome-wide level.MethodsWe adopted a gap analysis to screen for significant differential AS events (DASEs) associated with BLCA. DASEs with prognostic value for OS and the disease-free interval (DFI) were identified by Cox analysis. In addition, a differential AS network and AS clusters were identified using unsupervised cluster analysis. We examined differences in the sensitivity to chemotherapy and immunotherapy between BLCA patients with high and low overall survival (OS) risk.ResultsAn extensive number of DASEs (296) were found to be clinically relevant in BLCA. A prognosis model was established based prognostic value of OS and DFI. CUGBP elav-like family member 2 (CELF2) was identified as a hub splicing factor for AS networks. We also identified AS clusters associated with OS using unsupervised cluster analysis, and we predicted that the effects of cisplatin and gemcitabine chemotherapy would be different between high- and low-risk groups based on OS prognosis.ConclusionWe completed a comprehensive analysis of AS events in BLCA at the genome-wide level. The present findings revealed that DASEs and splicing factors tended to impact BLCA patient survival and sensitivity to chemotherapy drugs, which may provide novel prospects for BLCA therapies.

scholarly journals The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events

RNA Biology ◽  
2009 ◽  
Vol 6 (5) ◽  
pp. 546-562 ◽  
Author(s):  
Claude C. Warzecha ◽  
Shihao Shen ◽  
Yi Xing ◽  
Russ P. Carstens
Keyword(s):  
Alternative Splicing ◽  
Splicing Factors ◽  
Alternative Splicing Events

Identification of five long noncoding RNAs signature and risk score for prognosis of bladder urothelial carcinoma

2019 ◽  
Vol 121 (1) ◽  
pp. 856-866 ◽  
Author(s):  
Chuanjie Zhang ◽  
Zongtai Li ◽  
Jiateng Hu ◽  
Feng Qi ◽  
Xiao Li ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Risk Score ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Bladder Urothelial Carcinoma

scholarly journals Alternative Splicing Events in Tumor Immune Infiltration in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jian-yu Shi ◽  
Yan-yan Bi ◽  
Bian-fang Yu ◽  
Qing-feng Wang ◽  
Dan Teng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Alternative Splicing ◽  
High Risk ◽  
Risk Score ◽  
Immune Cell ◽  
Risk Model ◽  
Low Risk ◽  
Risk Scores ◽  
Immune Cell Infiltration ◽  
Immune Infiltration

Despite extensive research, the exact mechanisms involved in colorectal cancer (CRC) etiology and pathogenesis remain unclear. This study aimed to examine the correlation between tumor-associated alternative splicing (AS) events and tumor immune infiltration (TII) in CRC. We analyzed transcriptome profiling and clinical CRC data from The Cancer Genome Atlas (TCGA) database and lists of AS-related and immune-related signatures from the SpliceSeq and Innate databases, respectively to develop and validate a risk model of differential AS events and subsequently a TII risk model. We then conducted a two-factor survival analysis to study the association between TII and AS risk and evaluated the associations between immune signatures and six types of immune cells based on the TIMER database. Subsequently, we studied the distribution of six types of TII cells in high- and low-risk groups for seven AS events and in total. We obtained the profiles of AS events/genes for 484 patients, which included 473 CRC tumor samples and 41 corresponding normal samples, and detected 22581 AS events in 8122 genes. Exon Skip (ES) (8446) and Mutually Exclusive Exons (ME) (74) exhibited the most and fewest AS events, respectively. We then classified the 433 patients with CRC into low-risk (n = 217) and high-risk (n = 216) groups based on the median risk score in different AS events. Compared with patients with low-risk scores (mortality = 11.8%), patients with high-risk scores were associated with poor overall survival (mortality = 27.6%). The risk score, cancer stage, and pathological stage (T, M, and N) were closely correlated with prognosis in patients with CRC (P < 0.001). We identified 6479 differentially expressed genes from the transcriptome profiles of CRC and intersected 468 differential immune-related signatures. High-AS-risk and high-TII-risk predicted a poor prognosis in CRC. Different AS types were associated with different TII risk characteristics. Alternate Acceptor site (AA) and Alternate Promoter (AP) events directly affected the concentration of CD4T cells, and the level of CD8T cells was closely correlated with Alternate Terminator (AT) and Exon Skip (ES) events. Thus, the concentration of CD4T and CD8T cells in the CRC immune microenvironment was not specifically modulated by AS. However, B cell, dendritic cell, macrophage, and neutrophilic cell levels were strongly correlated with AS events. These results indicate adverse associations between AS event risk levels and immune cell infiltration density. Taken together, our findings show a clear association between tumor-associated alternative splicing and immune cell infiltration events and patient outcome and could form a basis for the identification of novel markers and therapeutic targets for CRC and other cancers in the future.

scholarly journals Systematic profiling of alternative splicing events and splicing factors in left- and right-sided colon cancer

Aging ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 8270-8293 ◽  
Author(s):  
Xiaoliang Huang ◽  
Jungang Liu ◽  
Xianwei Mo ◽  
Haizhou Liu ◽  
Chunyin Wei ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Alternative Splicing ◽  
Splicing Factors ◽  
Left And Right ◽  
Alternative Splicing Events
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