Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas

Lin, Peng; He, Rong‐Quan; Ma, Fuchao; Liang, Liang; He, Yun; Yang, Hong; Dang, Yi‐Wu; Chen, Gang

doi:10.1016/j.ebiom.2018.07.040

Cited by 53 publications

(64 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2017, Li et al pioneered an investigation of prognostic AS events to construct prognostic signatures for predicting the survival of non‐small cell lung cancer patients using TCGA data . Similar approaches were used to research other tumors, such as bladder cancer, prostate cancer, ovarian cancer, esophageal carcinoma, and gastrointestinal adenocarcinomas . These studies have applied AS to clinical practice regarding cancer, providing predictive references for prognosis at a molecular level.…”

Section: Discussionmentioning

confidence: 99%

Role of alternative splicing signatures in the prognosis of glioblastoma

Xie

Dang

et al. 2019

Cancer Medicine

Self Cite

View full text Add to dashboard Cite

Background Increasing evidence has validated the crucial role of alternative splicing (AS) in tumors. However, comprehensive investigations on the entirety of AS and their clinical value in glioblastoma (GBM) are lacking. Methods The AS profiles and clinical survival data related to GBM were obtained from The Cancer Genome Atlas database. Univariate and multivariate Cox regression analyses were performed to identify survival‐associated AS events. A risk score was calculated, and prognostic signatures were constructed using seven different types of independent prognostic AS events, respectively. The Kaplan‐Meier estimator was used to display the survival of GBM patients. The receiver operating characteristic curve was applied to compare the predictive efficacy of each prognostic signature. Enrichment analysis and protein interactive networks were conducted using the gene symbols of the AS events to investigate important processes in GBM. A splicing network between splicing factors and AS events was constructed to display the potential regulatory mechanism in GBM. Results A total of 2355 survival‐associated AS events were identified. The splicing prognostic model revealed that patients in the high‐risk group have worse survival rates than those in the low‐risk group. The predictive efficacy of each prognostic model showed satisfactory performance; among these, the Alternate Terminator (AT) model showed the best performance at an area under the curve (AUC) of 0.906. Enrichment analysis uncovered that autophagy was the most enriched process of prognostic AS gene symbols in GBM. The protein network revealed that UBC, VHL, KCTD7, FBXL19, RNF7, and UBE2N were the core genes in GBM. The splicing network showed complex regulatory correlations, among which ELAVL2 and SYNE1_AT_78181 were the most correlated (r = −.506). Conclusions Applying the prognostic signatures constructed by independent AS events shows promise for predicting the survival of GBM patients. A splicing regulatory network might be the potential splicing mechanism in GBM.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of alternative splicing signatures in the prognosis of glioblastoma

Xie

Dang

et al. 2019

Cancer Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…The pioneering work reported by Li et al () developed a powerful prognostic signature based on AS events in non‐small‐cell lung cancer. Subsequently, systematic profiling of prognostic AS signatures has been reported in esophageal carcinoma, ovarian cancer, papillary thyroid cancer, gastrointestinal adenocarcinomas as well as head neck cancer (Lin et al, ; Mao et al, ; Zhu, Chen, & Yong, ). Noticeably, comprehensive analyses of AS events in head neck squamous cell carcinoma (HNSCC) have been reported and predictive models based on AS have been established as prognostic predictors with high performance (Liang et al, ; Xing, Zhang, & Tong, ).…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, systematic profiling of prognostic AS signatures has been reported in esophageal carcinoma, ovarian cancer, papillary thyroid cancer, gastrointestinal adenocarcinomas as well as head neck cancer (Lin et al, 2018(Lin et al, , 2019Mao et al, 2019;Zhu, Chen, & Yong, 2018).…”

mentioning

confidence: 99%

Identification of a prognostic alternative splicing signature in oral squamous cell carcinoma

Zhang

Diao

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Alternative splicing (AS) is critically associated with tumorigenesis and patient's prognosis.Here, we systematically analyzed survival-associated AS signatures in oral squamous cell carcinoma (OSCC) and evaluated their prognostic predictive values. Survival-related AS events were identified by univariate and multivariate Cox regression analyses using OSCC data from the TCGA head neck squamous cell carcinoma data set. The Percent Spliced In calculated by SpliceSeq from 0 to 1 was used to quantify seven types of AS events. A predictive model based on AS events was constructed by least absolute shrinkage and selection operator Cox regression assay and further validated using a training-testing cohort design. Patient survival was estimated using the Kaplan-Meier method and compared with Log-rank test. The receiver operating characteristics curve area under the curves was used to evaluate the predictive abilities of these predictive models.Furthermore, gene-gene interaction networks and the splicing factors (SFs)-AS regulatory network was generated by Cytoscape. A total of 825 survival-related AS events within 719 genes were identified in OSCC samples. The integrative predictive model was better at predicting outcomes of patients as compared to those models built with the individual AS event. The predictive model based on three AS-related genes also effectively predicted patients' survival. Moreover, seven survival-related SFs were detected in OSCC including RBM4, HNRNPD, and HNRNPC, which have been linked to tumorigenesis. The SF-AS network revealed a significant correlation between survival-related AS genes and these SFs. Our findings revealed a systemic portrait of survival-associated AS events and the splicing network in OSCC, suggesting that AS events might serve as novel prognostic biomarkers and therapeutic targets for OSCC. K E Y W O R D Salternative splicing, oral squamous cell carcinoma, prognosis, splicing factor

show abstract

“…The feasibility of AS-based risk signature have been proved in non-small cell lung cancer, ovarian cancer, bladder cancer and gastrointestinal pan-adenocarcinomas [16][17][18][19], where AS-based risk signature have excellent distinguishing ability for the prognosis of low-risk and high-risk patients. Thus, we attempted to offer novel approach to prognostic stratification for RCC patients from the respective of AS and splicing factor.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide Analysis of the Alternative Splicing Profiles Revealed Novel Prognostic Index for Kidney Renal Cell Clear Cell Carcinoma

Huang

et al. 2020

J. Cancer

Self Cite

View full text Add to dashboard Cite

Alternative splicing (AS) is a major mechanism that greatly enhanced the diversity of proteome. Mounting evidence demonstrated that aberration of AS are important steps for the initiation and progression of human cancers. Here, we comprehensively investigated the association between whole landscape of AS profiles and the survival outcome of renal cell carcinoma (RCC) patients using RNA-seq data from TCGA SpliceSeq. Because of the limited number size of deaths in kidney chromophobe renal cell carcinoma (KICH) and papillary renal cell carcinoma (KIRP) TCGA cohorts, we only conducted survival analysis in kidney clear renal cell carcinoma (KIRC). We further constructed prognostic index (PI) based on prognosis-related AS events and built correlation network for splicing factors and prognosis-related AS events. According to the results, a total of 5351 AS events in 3522 genes were significantly correlated with the overall survival (OS) of kidney clear cell renal cell carcinoma (KIRC) patients. Seven of the PI models exhibited preferable prognosis-predicting capacity for KIRC with PI-ALL reaching the highest area under curve value of 0.875. The splicing regulatory network between splicing factors and prognosis-related AS events depicted a tangled web of relationships between them. One of the splicing factors: KHDRBS3 was validated by immunohistochemistry to be down-regulated in KIRC tissues. In conclusion, the powerful efficiency of risk stratification of PI models indicated the potential of AS signature as promising prognostic markers for KIRC and the splicing regulation network provided possible genetic mechanism of KIRC.

show abstract

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas

Cited by 53 publications

References 51 publications

Role of alternative splicing signatures in the prognosis of glioblastoma

Role of alternative splicing signatures in the prognosis of glioblastoma

Identification of a prognostic alternative splicing signature in oral squamous cell carcinoma

Genome-wide Analysis of the Alternative Splicing Profiles Revealed Novel Prognostic Index for Kidney Renal Cell Clear Cell Carcinoma

Contact Info

Product

Resources

About