Bioinformatic Analysis Using Online Databases

Gene expression data and clinical characteristics (tumor grade, age at diagnosis, survival time, censored status, and treatment history) were acquired from the Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn). Data from mRNAseq_325 (containing 325 samples) was used for the gene expression analysis of low-grade gliomas (LGGs, grade II) and high-grade gliomas (HGGs, grade III and IV GBM). mRNA-array_301 data (containing 301 samples) was employed for GBM subtypes. Other analyses were implemented using mRNAseq_693 data (containing 693 samples). Disease-specific overall survival (OS) was calculated from the date of diagnosis until disease-caused death or end of follow-up. Differences in expression features between different groups were determined using the Student’s t-tests. Kaplan−Meier curves were developed via GraphPad Prism 8 (GraphPad Software Inc., San Diego, CA, USA), comparing overall survival rates between patients with and without the genetic alterations of interest. The log rank tests were conducted to assess the prognostic significance. The detail information was supplemented in Supplementary Table S3 .

Clinical information for GBM patients (n = 41) and corresponding tumors (n = 42) was downloaded from the Ivy Glioblastoma Atlas Project (Ivy GAP) (43). The Ivy GAP RNAseq dataset was used to analyze CUL4B expression in different GBM regions. Detailed information of datasets was shown in Supplementary Table S4 .

mRNA expression profiles in {"type":"entrez-geo","attrs":{"text":"GSE72951","term_id":"72951"}}GSE72951 (44) from the publicly available the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo), which had been collected using the Illumina {"type":"entrez-geo","attrs":{"text":"GPL14951","term_id":"14951"}}GPL14951 platform (HumanHT-12 WG-DASL V4.0 R2 expression beadchip) were analyzed. {"type":"entrez-geo","attrs":{"text":"GSE72951","term_id":"72951"}}GSE72951 includes 112 GBM surgical specimens. mRNA expression profiles which had been collected using the {"type":"entrez-geo","attrs":{"text":"GPL8300","term_id":"8300"}}GPL8300 platform (Affymetrix Human Genome U95 Version 2 Array) in {"type":"entrez-geo","attrs":{"text":"GSE13041","term_id":"13041"}}GSE13041 (45), were analyzed. The {"type":"entrez-geo","attrs":{"text":"GSE13041","term_id":"13041"}}GSE13041 dataset includes 267 primary GBM surgical specimens. Detailed information of datasets was shown in Supplementary Table S5 .