Profiles of alternative splicing in colorectal cancer and their clinical significance: A study based on large-scale sequencing data

Xiong, Yong; Deng, Ying; Wang, Kang; Zhou, He; Zheng, Xiangru; Si, Liang-Yi; Fu, Zhongxue

doi:10.1016/j.ebiom.2018.09.021

Cited by 93 publications

(92 citation statements)

References 62 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we further analyzed the relevant clinical information (such as survival time, survival status, TNM, Age, etc) and found that some related information was not randomly distributed, such as survival status (alive or dead) in 4 clusters. In addition, there were significant differences between T and N. This was similar to the phenomenon found in the study by Xiong and colleagues 38 in rectal cancer. Therefore, we could also identify molecular subtype clusters associated with prognosis through AS events.…”

Section: Discussionsupporting

confidence: 89%

“…Through data mining, we can also systematically study RNA splicing disorders in cancer. By comparing different alternative splicing events between tumors and adjacent normal tissues, it has been established that survival‐related AS events are associated with a variety of tumors, such as glioblastoma, 35 breast cancer, 36 lung cancer, 37 and colorectal cancer 38 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic profiling of alternative splicing signature reveals prognostic predictor for prostate cancer

Zhao

Chang

et al. 2020

Cancer Science

View full text Add to dashboard Cite

Alternative splicing (AS) provides the primary mechanism for producing protein diversity. There is growing evidence that AS is involved in the development and progression of cancers. The rapid accumulation of high‐throughput sequencing technologies and clinical data sets offers an opportunity to systematically profile the relationship between mRNA variants and clinical outcomes. However, there is a lack of systematic analysis of AS in prostate cancer: Download RNA‐seq data and clinical information from The Cancer Genome Atlas (TCGA) data portal. Evaluate RNA splicing patterns by SpliceSeq and calculate splicing percentage (PSI) values. Different expressions were identified as differently expressed AS events (DEAs) based on PSI values. Bioinformatics methods were used for further analysis of DEAs and their splicing networks. Kaplan‐Meier, Cox proportional regression, and unsupervised cluster analysis were used to assess the correlation between DEAs and clinical characteristics. In total, 43 834 AS events were identified, of which 1628 AS events were differentially expressed. The parental genes of these DEAs played a significant role in the regulation of prostate cancer‐related processes. In total, 226 DEAs events were found to be associated with disease‐free survival. Four clusters of molecules with different survival modes were revealed by unsupervised cluster analysis of DEAs. AS events may be important determinants of prognosis and bio‐modulation in prostate cancer. In this study, we established strong prognostic predictors, discovered a splicing network that may be a potential mechanism, and provided further validated therapeutic targets.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Systematic profiling of alternative splicing signature reveals prognostic predictor for prostate cancer

Zhao

Chang

et al. 2020

Cancer Science

View full text Add to dashboard Cite

show abstract

“…To identify AS events with prognostic value that may serve as promising targets, gene network analysis by Cytoscape was performed including the top 300 survival related events, and several AS-related genes such as UBC, STAT3, and FYN were identi ed as hub genes. Then, we attempted to perform unsupervised analysis, which is considered as a better method to predict survival based on AS events [28]. However, the results showed that only one cluster was associated with survival status, which accounted for a small proportion of GBM patients.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Ren

Liu

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Aims: The purpose of this study was to depict alternative splicing (AS) profiles in GBM and identify their clinical significance in the progression of GBM. Materials and Methods: RNA sequence data and clinical information were downloaded from The Cancer Genome Atlas portal (https://portal.gdc.cancer.gov/projects). Genome-wide alternative splicing events were obtained using SpliceSeq tool. Analyses were performed using GraphPad Prism 7 and R software. Key findings: Univariate Cox analysis identified 2406 AS events with prognostic significance. We built an interaction network based on these survival-related AS events. Unsupervised clustering analysis showed that patients in cluster 2 had a better prognosis than those in other clusters. The prognostic splicing factors and AS events were used to generate a splicing network. Seven prognostic signatures, developed based on the top three survival-related AS events, predicted the survival risk and may serve as independent indicators of unfavorable prognosis. Among these risk signatures, only the alternate promoter (AP) signature was upregulated in the mesenchymal subtype, which is characterized by a complex immune microenvironment. A high AP risk score indicated an overloaded local immune response and enriched immune cell infiltration, which may accelerate the progression of GBM.Significance: AS-related signatures may serve as predictors of prognosis as well as provide treatment targets and guidance for GBM patients.

show abstract

“…Aberrant splicing events in CRC and/or other cancer types were identified using either microarray or RNA-seq techniques in the past [14][15][16][17]. The roles of AS in CRC were reported for individual genes: ITGA6 [18], MAP4K4 [19], EPDR1, ZNF518B [20], FIR [21], BRAF [22], Rac1 [23], OCT4 24], RON [25], CD44 [26,27], KRAS [28], ZNF148 [29], FAK [30].…”

Section: Introductionmentioning

confidence: 99%

Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer

Lian

Wang

Shen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Alternative splicing (AS) is an important mechanism of regulating eukaryotic gene expression. Understanding the most common AS events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC.Methods: Publicly available RNA-seq data of 28 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify AS events using PSI and DEXSeq methods. Result: The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified AS events in 9 genes in CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6). Except for CHEK1, all other 8 splicing events were confirmed by TCGA data with 382 CRC tumors and 51 normal controls. The combination of three splicing events was used to build a logistic regression model that can predict sample type (CRC or normal) with near perfect performance (AUC=1). Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The AS features of the 9 genes are highly consistent with previous reports and/or relevant to cancer biology. Conclusions: The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.

show abstract

Profiles of alternative splicing in colorectal cancer and their clinical significance: A study based on large-scale sequencing data

Cited by 93 publications

References 62 publications

Systematic profiling of alternative splicing signature reveals prognostic predictor for prostate cancer

Systematic profiling of alternative splicing signature reveals prognostic predictor for prostate cancer

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

Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer

Contact Info

Product

Resources

About