Combinations of four or more CpGs methylation present equivalent predictive value for MGMT expression and temozolomide therapeutic prognosis in gliomas

Chai, Rui‐Chao; Zhang, Ke‐Nan; Liu, Yuqing; Wu, Fan; Zhao, Zheng; Wang, Kuan‐Yu; Jiang, Tao; Wang, Yongzhi

doi:10.1111/cns.13040

Cited by 30 publications

(41 citation statements)

References 34 publications

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“…Based on the median risk value (23,26), patients in CGGA-RNAseq, TCGA-RNAseq, and TCGA microarray databases were divided into high-and low-risk groups. Kaplan-Meier survival curves were calculated and the log rank tests were conducted to assess the prognostic significance (13,27). Differences in clinicopathologic features between the groups were determined using the Student's t-or Chi-square tests.…”

Section: Resultsmentioning

confidence: 99%

Gene Expression Profiling Stratifies IDH-Wildtype Glioblastoma With Distinct Prognoses

Liu

et al. 2019

Front. Oncol.

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Objectives: In the present study, we aimed to determine the candidate genes that may function as biomarkers to further distinguish patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM), which are heterogeneous with respect to clinical outcomes. Materials and Methods: We selected 41 candidate genes associated with overall survival (OS) using univariate Cox regression from IDH-wildtype GBM patients based on RNA sequencing (RNAseq) expression data from the Chinese Glioma Genome Atlas (CGGA, n = 105) and The Cancer Genome Atlas (TCGA, n = 139) cohorts. Next, a sevengene-based risk signature was formulated according to Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm in the CGGA RNAseq database as a training set, while another 525 IDH-wildtype GBM patient TCGA datasets, consisting of RNA sequencing and microarray data, were used for validation. Patient survival in the low-and high-risk groups was calculated using Kaplan-Meier survival curve analysis and the log-rank test. Uni-and multivariate Cox regression analysis was used to assess the prognosis value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were performed for the functional analysis of the seven-gene-based risk signature. Results: We developed a seven-gene-based signature, which allocated each patient to a risk group (low or high). Patients in the high-risk group had dramatically shorter overall survival than their low-risk counterparts in three independent cohorts. Univariate and multivariate analysis showed that the seven-gene signature remained an independent prognostic factor. Moreover, the seven-gene risk signature exhibited a striking prognostic validity, with AUC of 78.4 and 73.9%, which was higher than for traditional "age" (53.7%, 62.4%) and "GBM sub-type" (57.7%, 52.9%) in the CGGA-and TCGA-RNAseq databases, respectively. Subsequent bioinformatics analysis predicted that the sevengene signature was involved in the inflammatory response, immune response, cell adhesion, and apoptotic process. Conclusions: Our findings indicate that the seven-gene signature could be a potential prognostic biomarker. This study refined the current classification system of IDH-wildtype GBM and may provide a novel perspective for the research and individual therapy of IDH-wildtype GBM.

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Section: Resultsmentioning

confidence: 99%

Gene Expression Profiling Stratifies IDH-Wildtype Glioblastoma With Distinct Prognoses

Liu

et al. 2019

Front. Oncol.

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“…Malignant progression and high recurrence rate render GBM the most lethal type of primary brain tumor. [35][36][37] In this study, we construct a 3-gene SPKKPs signature which could efficiently evaluate the risk of GBM patients and stratified these patients into two subgroups with distinct survival and clinicopathological features (MGMT promoter methylation status and subtypes). Several studies have shown the regulatory roles of SPKKPs family members in cancer biology.…”

Section: Discussionmentioning

confidence: 99%

Secretory Pathway Kinase FAM20C, a Marker for Glioma Invasion and Malignancy, Predicts Poor Prognosis of Glioma

Du¹,

Guan²,

Zhu³

et al. 2020

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“…In the CGGA cohort, both IDH1/2 mutation status and MGMT methylation status were detected by pyrosequencing, which is commonly used in clinical practice, following procedures described in our previous study [26, 27]. For the TCGA cohort, all molecular information was directly downloaded from the TCGA official website.…”

Section: Methodsmentioning

confidence: 99%

ADAMTSL4, a Secreted Glycoprotein, Is a Novel Immune-Related Biomarker for Primary Glioblastoma Multiforme

et al. 2019

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Background Researches on immunotherapy of glioblastoma multiforme (GBM, WHO grade IV) have increased exponentially in recent years. As a targeted therapy, a series of biomarkers have been identified in local tumor tissue, while circulating marker which could be detected in the body fluids is still lacking. ADAMTSL4, a secreted glycoprotein, was earlier found to play a critical role in a prognostic signature for primary GBM (pGBM). We aimed to investigate the role of ADAMTSL4 at transcriptome level and its relationship with clinical practice in pGBM. Methods A cohort of 88 pGBM patients with RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) was analyzed, and 168 pGBM patients from TCGA were included as validation. Several bioinformatic methods and predictive tools were applied to investigate the ADAMTSL4-associated immune microenvironment status. Results We found that ADAMTSL4 was enriched in GBM (WHO grade IV), especially for those with IDH1/2 wild-type and MGMT unmethylated groups. According to the TCGA classification scheme, ADAMTSL4 can act as a potential marker for subtypes with poorer prognosis. Bioinformatic analyses revealed that ADAMTSL4 was significantly correlated to the immune-related processes in GBM (WHO grade IV), especially representing the infiltration of immune cells and complicated tumor microenvironment. Clinically, high expression of ADAMTSL4 was an independent indicator for poor prognosis. Conclusion The expression of ADAMTSL4 is closely related to the clinicopathologic characteristics of pGBM. Meanwhile, it may play a critical role in immune-related processes. As a secreted glycoprotein, ADAMTSL4 is a promising circulating biomarker for pGBM, deserving further investigations.

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Combinations of four or more CpGs methylation present equivalent predictive value for MGMT expression and temozolomide therapeutic prognosis in gliomas

Abstract: Four-CpG combinations of pyrosequencing are sufficient for evaluating the methylation status of MGMT and predicting therapeutic prognosis in gliomas.

Cited by 30 publications

References 34 publications

Gene Expression Profiling Stratifies IDH-Wildtype Glioblastoma With Distinct Prognoses

Gene Expression Profiling Stratifies IDH-Wildtype Glioblastoma With Distinct Prognoses

<p>Secretory Pathway Kinase <em>FAM20C</em>, a Marker for Glioma Invasion and Malignancy, Predicts Poor Prognosis of Glioma</p>

ADAMTSL4, a Secreted Glycoprotein, Is a Novel Immune-Related Biomarker for Primary Glioblastoma Multiforme

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