scholarly journals Features of alternative splicing in stomach adenocarcinoma and their clinical implication: A research based on massive sequencing data

2020 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Qian Niu ◽  
Yun Han ◽  
Xingyu Liu ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
High Efficiency ◽  
Cox Regression ◽  
Area Under The Curve ◽  
The Cancer Genome Atlas ◽  
Regulation Mechanism ◽  
Sequencing Data ◽  
Cox Regression Analysis ◽  
Molecular Events ◽  
Stomach Adenocarcinoma

Abstract Background: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed.Methods: Within this work, genetic expression and clinical data of STAD were queried from The Cancer Genome Atlas (TCGA), and profiles of AS events were searched from the SpliceSeq database. Cox regression analysis found survival associated AS events. Finally, the splicing network was constructed to reflect the correlation between survival associated AS events and splicing factors (SF).Results: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events.Conclusions: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

scholarly journals Features of alternative splicing in stomach adenocarcinoma and their clinical implication: A research based on massive sequencing data

2020 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Qian Niu ◽  
Yun Han ◽  
Xingyu Liu ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
High Efficiency ◽  
Cox Regression ◽  
Area Under The Curve ◽  
The Cancer Genome Atlas ◽  
Regulation Mechanism ◽  
Sequencing Data ◽  
Cox Regression Analysis ◽  
Molecular Events ◽  
Stomach Adenocarcinoma

Abstract Background: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed.Methods: Within this work, genetic expression and clinical data of STAD were queried from The Cancer Genome Atlas (TCGA), and profiles of AS events were searched from the SpliceSeq database. Cox regression analysis found survival associated AS events. Finally, the splicing network was constructed to reflect the correlation between survival associated AS events and splicing factors (SF).Results: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events.Conclusions: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

scholarly journals Features of alternative splicing in stomach adenocarcinoma and their clinical implication: A research based on massive sequencing data

2020 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Qian Niu ◽  
Yun Han ◽  
Xingyu Liu ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
High Efficiency ◽  
Cox Regression ◽  
Area Under The Curve ◽  
The Cancer Genome Atlas ◽  
Regulation Mechanism ◽  
Sequencing Data ◽  
Cox Regression Analysis ◽  
Molecular Events ◽  
Stomach Adenocarcinoma

Abstract Background: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed. Methods: Within this work, genetic expression and clinical data of STAD were queried from The Cancer Genome Atlas (TCGA), and profiles of AS events were searched from the SpliceSeq database. Cox regression analysis found survival associated AS events. Finally, the splicing network was constructed to reflect the correlation between survival associated AS events and splicing factors (SF). Results: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events. Conclusions: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

scholarly journals Features of alternative splicing in stomach adenocarcinoma and their clinical implication: A research based on massive sequencing data

2020 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Shengling Ma ◽  
Qian Niu ◽  
Yun Han ◽  
Xingyu Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Operating Characteristic ◽  
High Efficiency ◽  
Area Under The Curve ◽  
Regulation Mechanism ◽  
Sequencing Data ◽  
Molecular Events ◽  
Massive Sequencing ◽  
Stomach Adenocarcinoma ◽  
Prognostic Prediction

Abstract Background: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed.Results: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events.Conclusions: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

scholarly journals Features of alternative splicing in stomach adenocarcinoma and their clinical implication: A research based on massive sequencing data

2020 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Shengling Ma ◽  
Qian Niu ◽  
Yun Han ◽  
Xingyu Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Operating Characteristic ◽  
High Efficiency ◽  
Area Under The Curve ◽  
Regulation Mechanism ◽  
Sequencing Data ◽  
Molecular Events ◽  
Massive Sequencing ◽  
Stomach Adenocarcinoma ◽  
Prognostic Prediction

Abstract Background: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed.Results: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events.Conclusions: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

scholarly journals Features of alternative splicing in stomach adenocarcinoma and their clinical implication: A research based on massive sequencing data

2020 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Shengling Ma ◽  
Qian Niu ◽  
Yun Han ◽  
Xingyu Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Operating Characteristic ◽  
High Efficiency ◽  
Area Under The Curve ◽  
Regulation Mechanism ◽  
Sequencing Data ◽  
Molecular Events ◽  
Massive Sequencing ◽  
Stomach Adenocarcinoma ◽  
Prognostic Prediction

Abstract Background: Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed.Results: 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events.Conclusions: In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.

scholarly journals Identification of prognostic alternative splicing events in sarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongshuai Li ◽  
Jie Yang ◽  
Guohui Yang ◽  
Jia Ren ◽  
Yu Meng ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Functional Roles ◽  
Cancer Pathogenesis ◽  
Rare Malignancy

AbstractSarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.

scholarly journals Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
High Efficiency ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Sequencing Data ◽  
Cox Regression Analysis

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

scholarly journals Prognostic Signatures of Alternative Splicing Events in Esophageal Carcinoma Based on TCGA Splice-Seq Data

2021 ◽  
Vol 11 ◽  
Author(s):  
Ping Ye ◽  
Yan Yang ◽  
Liqiang Zhang ◽  
Guixi Zheng
Keyword(s):  
Alternative Splicing ◽  
Esophageal Carcinoma ◽  
Cox Regression ◽  
Donor Site ◽  
Area Under The Curve ◽  
Clinical Information ◽  
Roc Curves ◽  
The Cancer Genome Atlas ◽  
Acceptor Site ◽  
Cox Regression Analysis

An alternative splicing (AS) event is a highly complex process that plays an essential role in post-transcriptional gene expression. Several studies have suggested that abnormal AS events were the primary element in the pathological process of cancer. However, few works are dedicated to the study of AS events in esophageal carcinoma (EC). In the present study, clinical information and RNA-seq data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The percent spliced in (PSI) values of AS events were acquired from the TCGA Splice-seq. A total of 183 EC patients were enrolled in this study, and 2,212 AS events were found significantly associated with the overall survival of these patients by univariate Cox regression analysis. The prognostic signatures based on AS events were built by multivariate Cox analysis. Receiver operating characteristic (ROC) curves displayed that the area under the curve (AUC) of the following prognostic signatures, including exon skip (ES), alternate terminator (AT), alternate acceptor site (AA), alternate promoter (AP), alternate donor site (AD), retained intron (RI), and total events, was greater than 0.8, suggesting that these seven signatures had valuable prognosis prediction capacity. Finally, the risk score of prognostic signatures was indicated as an independent risk factor of survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the function of splicing factors (SFs) that were associated with AS events. Also, the interactive network between AS events and SFs identified several hub genes and AS events which need further study. This was a comprehensive study that explored prognosis-related AS events and established valuable prognosis signatures in EC patients. The network of interactions between AS events and SFs might offer novel insights into the fundamental mechanisms of tumorigenesis and progression of EC.

scholarly journals Genome-Wide Analysis of Prognostic Alternative Splicing Signature and Splicing Factors in Lung Adenocarcinoma

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1300
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Hui-Shan Chiang ◽  
Ju-Chen Yen ◽  
Ya-Ting Lee ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Splicing Factors ◽  
Cox Regression Analysis ◽  
Underlying Mechanisms

Analysis of The Cancer Genome Atlas data revealed that alternative splicing (AS) events could serve as prognostic biomarkers in various cancer types. This study examined lung adenocarcinoma (LUAD) tissues for AS and assessed AS events as potential indicators of prognosis in our cohort. RNA sequencing and bioinformatics analysis were performed. We used SUPPA2 to analyze the AS profiles. Using univariate Cox regression analysis, overall survival (OS)-related AS events were identified. Genes relating to the OS-related AS events were imported into Cytoscape, and the CytoHubba application was run. OS-related splicing factors (SFs) were explored using the log-rank test. The relationship between the percent spliced-in value of the OS-related AS events and SF expression was identified by Spearman correlation analysis. We found 1957 OS-related AS events in 1151 genes, and most were protective factors. Alternative first exon splicing was the most frequent type of splicing event. The hub genes in the gene network of the OS-related AS events were FBXW11, FBXL5, KCTD7, UBB and CDC27. The area under the curve of the MIX prediction model was 0.847 for 5-year survival based on seven OS-related AS events. Overexpression of SFs CELF2 and SRSF5 was associated with better OS. We constructed a correlation network between SFs and OS-related AS events. In conclusion, we identified prognostic predictors using AS events that stratified LUAD patients into high- and low-risk groups. The discovery of the splicing networks in this study provides an insight into the underlying mechanisms.

scholarly journals Identification of prognostic and bone metastatic alternative splicing signatures in bladder cancer

2020 ◽  
Author(s):  
Runzhi Huang ◽  
Jiayao Zhang ◽  
Tianjing Wang ◽  
Jingyi Jia ◽  
Dianwen Song ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Alternative Splicing ◽  
Bone Metastasis ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Cox Regression Analysis ◽  
Predict Model ◽  
Glycosphingolipid Biosynthesis

Abstract Background ： Bladder cancer, originating from the epithelium of the urinary bladder, was the second most common malignancy in the urinary system with a high metastasis rate and poor post-metastasis prognosis. Alternative splicing events (ASEs) were regarded as important markers of tumor progression and prognosis, however, their roles in bladder cancer bone metastasis haven’t been recognized. Methods ： In order to explore the mechanism of ASEs in bladder cancer bone metastasis, we downloaded the RNA sequencing data and ASEs data of 412 samples of primary BLCAs from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. The Cox regression analysis was used to identify overall survival-related ASEs (OS-SEs), then, based on the OS-SEs screened by Lasso regression, we constructed the predict model. Finally, univariate and multivariate independent prognostic analysis were performed to prove it as an independent prognostic factor. Results ： In this study, a predict model of OS in BLCA was constructed and the Area Under Curve of the model was 0.581. Its risk score was also proved to be an independent predictor with the good accuracy (P < 0.001). Among identified 390 SFs, Junction plakoglobin (JUP) was significantly correlated with overall survival and bone metastasis. In co-expression analysis, the co-expression pathway of ITGB4 was the glycosphingolipid biosynthesis ganglio series. Conclusions ： We speculated that JUP regulating the ITGB4 might play a key role in bone metastasis of bladder cancer through the glycosphingolipid biosynthesis ganglio series pathway (R = 0.220, P < 0.001), which was also related to prognosis.

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