High EMP3 expression might independently predict poor overall survival in glioblastoma and its expression is related to DNA methylation

Yue, Hongya; Xu, Qun; Xie, Shugang

doi:10.1097/md.0000000000009538

Cited by 18 publications

(23 citation statements)

References 27 publications

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“…Previous results suggested that the expression of EMP3 in glioma patients was controlled by DNA methylation [29]. We found that DNA methylation intensity of EMP3 gene was lower in old LGG patients, compared with young LGG patients (P=3.71e-05) ( Figure 4B).…”

Section: Dna Methylation Profiles Of Age Related Genes In Lgg Patientssupporting

confidence: 50%

“…EMP3 was one of the hub genes in this network. Previous results suggested that EMP3 was a critical biomarker in glioma prognosis [28][29][30][31][32]. EMP was connected with TIMP1 and SERPINE1 and SERPINE1 was connected with IGFBP2 ( Figure 3D).…”

Section: Validation Of Age Related Genes In Glioma Patients Derived Fmentioning

confidence: 65%

“…The prognostic effects of EMP3 [28][29][30][31][32] and IGFBP2 [33][34][35] in glioma patients are extensively studied. Here, we find two EMP3 and IGFBP2 associated genes TIMP1 and SERPINE1 are also suitable biomarkers for prognosis of glioma patients.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of age related genes in patients with lower grade glioma

Wang¹,

Wang²,

Xu³

et al. 2020

J. Cancer

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Objective: To analyze the prognostic effects of age in different tumor types and determine the prognostic significance of age related genes in patients with lower grade glioma (LGG). Methods: The relationships between age and tumor overall survival were determined by Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset. The age related genes were identified using TCGA RNA-seq data. Univariate and multivariate cox regression were used to determine the prognostic significance of age related genes. The results derived from TCGA dataset were further validated using Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) datasets. Results: Age at initial pathologic diagnosis was most associated with the overall survival of LGG patients than other types of tumor patients. Age related genes EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in old LGG patients. The hypo-methylations of EMP3 and SERPINE1 were contributing to the high expressions of EMP3 and SERPINE1 in old LGG patients. Also, EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in LGG tumor tissues, compared with normal brain tissues. Moreover, high expressions of IGFBP2, EMP3, TIMP1 and SERPINE1 were associated with the worse prognosis of LGG patients. Furthermore, we demonstrated that EMP3 and SERPINE1 were connected with each other and the combination of EMP3 and SERPINE1 had better prognostic effects in glioma patients. Conclusions: Age related genes IGFBP2, EMP3, TIMP1 and SERPINE1 have significant prognostic effects in LGG patients.

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Section: Dna Methylation Profiles Of Age Related Genes In Lgg Patientssupporting

confidence: 50%

Section: Validation Of Age Related Genes In Glioma Patients Derived Fmentioning

confidence: 65%

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Prognostic significance of age related genes in patients with lower grade glioma

Wang¹,

Wang²,

Xu³

et al. 2020

J. Cancer

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“…Of particular interest is EMP3’s role in cancer development and progression. While several studies have suggested EMP3 to be a tumor suppressor, others have inversely proposed EMP3 to be an oncogene and promoter of tumor progression . The apparent discrepancy indicates that EMP3 can either augment or repress oncogenic signaling depending on the genetic background of the tumor and the pathways it is driven by.…”

Section: Discussionmentioning

confidence: 99%

“…EMP3 promoter methylation was significantly associated with IDH1/2 mutations and was a favorable prognostic marker in patients with oligodendroglial tumors . Analogous, in glioblastoma low EMP3 expression also was a favorable prognostic marker, while high expression was associated with shorter patient survival …”

Section: Introductionmentioning

confidence: 90%

Characterization of the epithelial membrane protein 3 interaction network reveals a potential functional link to mitogenic signal transduction regulation

Christians

Poisel

Hartmann

et al. 2019

Intl Journal of Cancer

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Epithelial Membrane Protein 3 (EMP3), a 4‐transmembrane glycoprotein, first gained attention as a putative tumor suppressor. Accumulating evidence, however, points to a more tumor promotive function of EMP3. The biological function of EMP3 remains largely unclear. To elucidate more of EMP3’s interaction network, we performed a Yeast‐Two‐Hybrid (Y2H) screening, followed by validation of candidate interactors by Biomolecular Fluorescence Complementation (BiFC) and Proximity Ligation Assay (PLA). Furthermore, we generated stable EMP3 knockdown cell lines and measured cell proliferation, migration and sensitivity to apoptosis induction as well as the expression and activation levels of important signal pathway components. The Y2H screening yielded 10 novel interactions of EMP3, eight of which could also be detected by BiFC and PLA interaction assays. All newly discovered interaction partners are involved in signaling or trafficking regulation. Most notably, FLOT1 and HTATIP2 have well described roles in the regulation of EGFR signaling. In addition, knockdown of EMP3 resulted in reduced levels of p‐AKT, p‐ERK and p‐EGFR, attenuated cell proliferation and migration and sensitized cells to apoptosis induction by TRAIL and Staurosporine. Based on these observations we hypothesize that EMP3 might be involved in the regulation of receptor‐tyrosine‐kinase mediated mitogenic signaling.

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A 4‐gene panel predicting the survival of patients with glioblastoma

Guo

2019

J of Cellular Biochemistry

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Background To identify independently prognostic gene panel in patients with glioblastoma (GBM). Materials and methods The Cancer Genome Atlas (TCGA)‐GBM was used as a training set and a test set. GSE13041 was used as a validation set. Survival associated differentially expression genes (DEGs), derived between GBM and normal brain tissue, was obtained using univariate Cox proportional hazards regression model and then was included in a least absolute shrinkage and selection operator penalized Cox proportional hazards regression model. Thus, a 4‐gene prognostic panel was developed based on the risk score for each patient in that model. The prognostic role of the 4‐gene panel was validated using univariate and multivariable Cox proportional hazards regression model. Results A total of 686 patients with GBM were included in our study; 724 DEGs was identified, 133 of which was significantly correlated with the overall survival (OS) of patients with GBM. A 4‐gene panel including NMB, RTN1, GPC5, and epithelial membrane protein 3 (EMP3) was developed. Kaplan‐Meier survival analysis suggested that patients in the 4‐gene panel low risk group had significantly better OS than those in the 4‐gene panel high risk group in the training set (hazard ratio [HR] = 0.3826; 95% confidence interval [CI]: 0.2751‐0.532; P < 0.0001), test set (HR = 0.718; 95% CI: 0.5282‐0.9759; P = 0.033) and the independent validation set (HR = 0.6898; 95% CI: 0.4872‐0.9766; P = 0.035). Both univariate and multivariable Cox proportional hazards regression analysis suggested that the 4‐gene panel was independent prognostic factor for GBM in the training set. Conclusion We developed and validated 4‐gene panel that was independently correlated with the survival of patients with GBM.

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High EMP3 expression might independently predict poor overall survival in glioblastoma and its expression is related to DNA methylation

Cited by 18 publications

References 27 publications

Prognostic significance of age related genes in patients with lower grade glioma

Prognostic significance of age related genes in patients with lower grade glioma

Characterization of the epithelial membrane protein 3 interaction network reveals a potential functional link to mitogenic signal transduction regulation

A 4‐gene panel predicting the survival of patients with glioblastoma

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