OncoTargets and Therapy (Jul 2020)
Low Expression of APOB mRNA or Its Hypermethylation Predicts Favorable Overall Survival in Patients with Low-Grade Glioma
Abstract
Chong Han,1,* Yang He,1,2,* Lifen Chen,3,* Jie Wang,4 Song Jiao,1 Xiangping Xia,1 Gang Li,1 Shengtao Yao1 1Department of Cerebrovascular Disease, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People’s Republic of China; 2Department of Neurosurgery, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, People’s Republic of China; 4Department of Oncology, Hubei General Hospital, Wuhan, Hubei 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengtao YaoDepartment of Cerebrovascular Disease, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaEmail [email protected]: This study was performed to explore the clinical and prognostic significance of APOB mRNA expression, DNA methylation and APOB mutation in patients with low-grade glioma (LGG).Methods: Bioinformatic analysis was conducted using genomic, clinical and survival data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Serum APOB protein levels were measured via immunoturbidimetry in 150 patients with LGG and 100 healthy controls from Hubei General Hospital.Results: There was a negative association between the levels of APOB mRNA and DNA methylation (r=− 0.355, P< 0.0001) in patients with LGG from the TCGA database. Additionally, LGG patients with low levels of APOB mRNA exhibited better overall survival (OS) than those with high levels of APOB mRNA (HR=0.637, P=0.0085). The survival time of LGG patients with APOB hypermethylation was markedly longer than that of patients with APOB hypomethylation (HR=0.423, P=0.0185). The prognostic significance of APOB mRNA and DNA methylation was also validated with the CGGA cohort, and a similar conclusion was reached. APOB gene mutations were observed in 3% of patients with LGG from the TCGA database, and no association was detected between APOB mutations and OS (P=0.164). Furthermore, the levels of APOB protein were much lower in patients with LGG than in normal individuals (P=0.0022), and the expression of APOB protein was markedly different among groups when stratified by histological type (P< 0.0001) and histological-molecular classification (P< 0.0001).Conclusion: APOB mRNA expression is negatively regulated by DNA methylation in patients with LGG. Low expression or hypermethylation of APOB might predict relatively favorable survival in patients with LGG.Keywords: low-grade glioma, APOB, prognosis, methylation, bioinformatic analysis
