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

Abstract

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

Knockdown of LINC00662 represses AK4 and attenuates radioresistance of oral squamous cell carcinoma

“…However, LINC00662 had no regulatory effects on hnRNPC expression. hnRNPC is a survival-related splicing factor in OSCC [18], and served as the tumor facilitator in non-small cell lung cancer [33], ovarian cancer [16]. The hnRNPC protein is one of the Fig.…”

“…In past researches, hnRNPC has been illustrated as pivotal mediators in human diseases, including carcinomas [16,17]. Besides, hnRNPC is identified as survival-related splicing factor in OSCC [18]. However, the specific functional role and underlying mechanism of hnRNPC in OSCC was uncertain.…”

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Oral Squamous Cell Carcinoma

“…A previous study also develops an AS-based prognostic model with good performance (AUC = 0.891 and 0.70 for training and validation cohort, respectively) ( 20 ). However, the TCGA OSCC cohort is randomly and equally split into the training and the validation cohort in this former analysis, which is not recommended in the TROPORT statement ( 21 ).…”

Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells

“…Our research focused on the prognostic significance of AS events in sarcoma patients. Although the prognostic ability of AS events have been widely confirmed in other cancers [ 14 , 19 – 23 , 34 – 36 ], the association of AS events in sarcoma patients remains unclear. In our study, 1945 AS events were determined as OS-related AS events and 1831 AS events were determined as DFS-related AS events.…”

“…More importantly, with the development of high-throughput sequencing, many studies have focused on comprehensive genome-wide profiling of AS events in cancer and confirmed that AS events can be used as robust prognostic biomarkers. For example, Zhang et al [ 19 ] studied 330 oral squamous cell carcinoma patients, and a AS event-based signature was established and validated. In addition, the AS-splicing factor (SF) regulatory network was also established.…”