AUTHOR=Huang Runzhi , Li Zhenyu , Li Chen , Wang Guanghua , Yan Penghui , Peng Li , Wang Jiaqi , Zhu Xiaolong , Hu Peng , Zhang Junfang , Chang Zhengyan , Huang Zongqiang , Cheng Liming , Zhang Jie 

TITLE=Germ Cell-Specific Gene 1-Like Protein Regulated by Splicing Factor CUGBP Elav-Like Family Member 5 and Primary Bile Acid Biosynthesis are Prognostic in Glioblastoma Multiforme

JOURNAL=Frontiers in Genetics

VOLUME=Volume 10 - 2019

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01380

DOI=10.3389/fgene.2019.01380

ISSN=1664-8021

ABSTRACT=Abstract Background: Alternative splicing (AS) modifies 92-94% human genes, abnormal splicing events might relate to tumor development and invasion. Glioblastoma Multiforme (GBM) is a fatal, invasive and malignant tumor in nervous system. The recurrence and development lead to poor prognosis. However, few studies have focused on AS in GBM. Methods: RNA-seq and Alternative splicing events (ASEs) data of GBM samples were downloaded from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases, respectively. Firstly, the Cox regression analysis was utilized to identify the overall survival splicing events (OSSEs). Secondly, we constructed a multivariable model and accessed the prognostic value of risk score. Then, we co-expressed a network between splicing factors (SFs) and overall survival alternative splicing events (OS-SEs). Additionally, we explored the potential prognostic pathways and constructed a network between these pathways and OS-SEs. Ultimately, multidimension validation was applied. Results: In total, 1,062 OS-SEs were selected by Cox regression. Then, by Lasso regression, 11 OS-SEs were integrated in a multivariate model. The area under the curve (AUC) of receiver operator characteristic (ROC) curve was 0.861. In addition, the risk score was an independent prognostic factor (P < 0.001). What's more, in the network of SFs and ASEs, CELF5 positively and negatively regulated GSG1L|35696|AP and GSG1L|35698|AP (P < 0.001, R = 0.511 and = -0.492). Additionally, GSG1L|35696|AP (P = 0.006) and GSG1L|35698|AP (P = 0.007) showed significant relationship with cancer status. Eventually, prognostic KEGG pathways were selected by GSVA. And the primary bile acid synthesis (P < 0.001, R = 0.420) was the significant pathway co-expressed with Germ Cell-Specific Gene 1-Like Protein (GSG1L).Based on the comprehensive bioinformatics analysis, we proposed that aberrant splicing factor CUGBP Elav-like family member 5 (CELF5) positively and negatively regulated ASE of GSG1L and the primary bile acid synthesis pathway might play an important role in tumorgenesis and prognosis of GBM.