Highlight
- •A four-gene signature (ALDOC, APOBEC3C, ANXA1 and ARPP21) was established for LGGs with MGMT promoter methylated.
- •The signature can divide LGGs with MGMT promoter methylated into low and high risk groups independently.
- •The OS and clinicopathologic factors of two groups were quite different.
Abstract
Due to the varied overall survival (OS), limited studies focus on the factors that
affect the prognosis for lower grade glioma patients (LGGs) with MGMT promoter methylated.
A total of 579 samples (TCGA LGGs 456; CGGA LGGs 123) were included to identify potential
genes for LGGs with MGMT promoter methylated. All bioinformatics analyses were conducted
using SPSS software and GraphPad Prism 6. Based on COX regression analysis, we established
a four-gene signature (ALDOC, APOBEC3C, ANXA1 and ARPP21) and divided LGGs into two
groups based on median risk score. The OS of LGGs in high risk group was shorter than
low risk group (P < 0.0001). Furthermore, the OS in high risk group were shorter than
low risk group in Grade II and III, respectively (P = 0.0003; P = 0.0104). It showed
that the signature was an independent prognosis factor on multivariate Cox regression
analysis (P = 0.033). Patients in high group tended to displayed high grade (GIII),
IDH1 wild type and mesenchymal subtype preference. Four-gene signature was discovered
for LGGs with MGMT promoter methylated. Our findings suggested that the four genes
could serve as prognostic biomarkers.
Keywords
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References
- Molecular diagnostics of gliomas.Arch Pathol Lab Med. 2011; 135: 558-568
- Prevalence estimates for primary brain tumors in China: a multi-center cross-sectional study.Chin Med J. 2011; 124: 2578-2583
- Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.N Engl J Med. 2005; 352: 987-996
- Management and survival rates in patients with glioma in China (2004–2010): a retrospective study from a single-institution.J Neurooncol. 2013; 113: 259-266
- CGCG clinical practice guidelines for the management of adult diffuse gliomas.Cancer Lett. 2016; 375: 263-273
- IDH1 and IDH2 mutations in gliomas.N Engl J Med. 2009; 360: 765-773
- Correlation of IDH1/2 mutation with clinicopathologic factors and prognosis in anaplastic gliomas: a report of 203 patients from China.J Cancer Res Clin Oncol. 2014; 140: 45-51
- Chromosome 1p loss: a favorable prognostic factor in low-grade gliomas.Ann Neurol. 2005; 58: 322-326
- Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.N Engl J Med. 2000; 343: 1350-1354
- A practical review of prognostic correlations of molecular biomarkers in glioblastoma.Neurosurg Focus. 2015; 38: E4
- Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity.J Clin Oncol. 2008; 26: 4189-4199
- O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy.Br Med Bull. 2008; 85: 17-33
- MGMT gene silencing and benefit from temozolomide in glioblastoma.N Engl J Med. 2005; 352: 997-1003
- Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide.J Clin Oncol. 2007; 25: 1470-1475
- Methylation of O6-methylguanine DNA methyltransferase and loss of heterozygosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival.Clin Cancer Res. 2007; 13: 2606-2613
- Methylation associated genes contribute to the favorable prognosis of gliomas with isocitrate dehydrogenase 1 mutation.Am J Cancer Res. 2015; 5: 2745-2755
- Correlation of IDH1 mutation with clinicopathologic factors and prognosis in primary glioblastoma: a report of 118 patients from China.PLoS One. 2012; 7e30339
- Association between small heat shock protein B11 and the prognostic value of MGMT promoter methylation in patients with high-grade glioma.J Neurosurg. 2016; 125: 7-16
- HDAC4, a prognostic and chromosomal instability marker, refines the predictive value of MGMT promoter methylation.J Neurooncol. 2015; 122: 303-312
- Prognostic value of a nine-gene signature in glioma patients based on mRNA expression profiling.CNS Neurosci Ther. 2014; 20: 112-118
- Identification of high risk anaplastic gliomas by a diagnostic and prognostic signature derived from mRNA expression profiling.Oncotarget. 2015; 6: 36643-36651
- LncRNA profile study reveals four-lncRNA signature associated with the prognosis of patients with anaplastic gliomas.Oncotarget. 2016; 7: 77225-77236
- Suppression of fructose-bisphosphate aldolase C expression as a predictor of advanced oral squamous cell carcinoma.Head Neck. 2016; 38: E1075-E1085
- Glycolysis and the pentose phosphate pathway are differentially associated with the dichotomous regulation of glioblastoma cell migration versus proliferation.Neuro Oncol. 2016; 18: 1219-1229
- The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals.BMC Mol Biol. 2008; 9: 104
- Correlation of APOBEC3 in tumor tissues with clinico-pathological features and survival from hepatocellular carcinoma after curative hepatectomy.Int J Clin Exp Med. 2015; 8: 7762-7769
- Annexin 1: the new face of an old molecule.FASEB J. 2007; 21: 968-975
- The role of annexins in tumour development and progression.J Pathol. 2008; 216: 131-140
- Annexin A1 is associated with gastric cancer survival and promotes gastric cancer cell invasiveness through the formyl peptide receptor/extracellular signal-regulated kinase/integrin beta-1-binding protein 1 pathway.Cancer. 2012; 118: 5757-5767
- Knockdown of ANXA1 suppresses the biological behavior of human NSCLC cells in vitro.Mol Med Rep. 2016; 13: 3858-3866
- Loss of SNAIL regulated miR-128-2 on chromosome 3p22.3 targets multiple stem cell factors to promote transformation of mammary epithelial cells.Cancer Res. 2012; 72: 6036-6050
- A three-gene signature for prognosis in patients with MGMT promoter-methylated glioblastoma.Oncotarget. 2016; 7: 69991-69999
Article info
Publication history
Published online: March 27, 2020
Accepted:
March 20,
2020
Received:
August 29,
2019
Identification
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