Comprehensive development and validation of gene signature for predicting survival in patients with glioblastoma

Abstract

Glioblastoma (GBM) is the most common brain tumor, with rapid proliferation and fatal invasiveness. Large-scale genetic and epigenetic profiling studies have identified targets among molecular subgroups, yet agents developed against these targets have failed in late clinical development. We obtained the genomic and clinical data of GBM patients from the Chinese Glioma Genome Atlas (CGGA) and performed the least absolute shrinkage and selection operator (LASSO) Cox analysis to establish a risk model incorporating 17 genes in the CGGA693 RNA-seq cohort. This risk model was successfully validated using the CGGA325 validation set. Based on Cox regression analysis, this risk model may be an independent indicator of clinical efficacy. We also developed a survival nomogram prediction model that combines the clinical features of OS. To determine the novel classification based on the risk model, we classified the patients into two clusters using ConsensusClusterPlus, and evaluated the tumor immune environment with ESTIMATE and CIBERSORT. We also constructed clinical traits-related and co-expression modules through WGCNA analysis. We identified eight genes (ANKRD20A4, CLOCK, CNTRL, ICA1, LARP4B, RASA2, RPS6, and SET) in the blue module and three genes (MSH2, ZBTB34, and DDX31) in the turquoise module. Based on the public website TCGA, two biomarkers were significantly associated with poorer OS. Finally, through GSCALite, we re-evaluated the prognostic value of the essential biomarkers and verified MSH2 as a hub biomarker.

SARS-CoV-2 Pattern Provides a New Scoring System and Predicts the Prognosis and Immune Therapeutic Response in Glioma

“…These data strongly suggest that LARP4B acts as a tumor-suppressor gene of gliomas, as confirmed in our work, as LARP4B expression was negatively correlated with SC2I. Interestingly, there were also reports of LARP4B helping to predict prognosis and immunotherapy in glioma patients [ 33 , 34 ]. In summary, LARP4B is a tumor-suppressor gene of glioma; the potential mechanisms involved, however, remain to be probed further.…”

Molecular and clinical characterization of ANG expression in gliomas and its association with tumor-related immune response

“…Molecularly, the correlation between ANG and glioma malignancy was further explored through the perspective of genomic alterations. High-ANG was significantly associated with high amplification in multiple oncogenic drivers, including EGFR, CDK4, FIP1L1, PDGFRA, CHIC2, PIK3C2B, MDM4, MBD6, and DDIT3 ( 53 ), and with more frequent deletions in tumor-suppressing genes like CDKN2A, CDKN2B, MTAP, MLLT3, and PTEN ( 54 ). Moreover, high frequent mutations of PTEN, EGFR, NF1, RB1, and KEL, which corresponded to worse prognosis ( 55 ), were observed among the higher-ANG group.…”

“…ANG has been implicated in the pathogenesis of multiple malignant tumors, except for gliomas. To integratively demonstrate and characterize the ANG expression in whole-grade gliomas molecularly and clinically, we conducted this comprehensive analysis based on a total of 1,323 glioma samples from three independent glioma datasets of CGGA301, TCGA, and CGGA325, with which we would like to perform 3-dataset cross-validation to generate more robust results (51)(52)(53). Discoveries from CGGA301 as a discovery dataset were further validated in two independent datasets, including TCGA and CGGA325 datasets.…”

Disease-Based Prognostication: Neuro-Oncology

“…49 Recent studies have begun to include various biomarkers and genomics to strengthen the algorithms. Studies have implicated MSH2, which plays a key role in DNA mismatch repair, as having a potential predictive role, 50 as well as immune-related genes. 51,52 Male glioblastoma patients have a lower OS compared with women.…”