PPIC, EMP3 and CHI3L1 Are Novel Prognostic Markers for High Grade Glioma

Gao, Yuanfeng; Zhu, Tao; Mao, Chen-Xue; Liu, Zhixiong; Wang, Zhibin; Mao, Xiao‐Yuan; Li, Ling; Yin, Ji‐Ye; Zhou, Hong‐Hao; Liu, Zhao‐Qian

doi:10.3390/ijms17111808

Cited by 45 publications

(36 citation statements)

References 40 publications

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“…Previous studies reported that CpG island hypermethylation in the EMP3 promoter region is frequent in LGGs [28-30]. Moreover, EMP3 promoter hypermethylation is associated with a favorable prognostic significance in OS in patients with oligodendroglial and glioblastoma [29, 31, 32]. In line with previous studies, we found that promoter methylation in EMP3 correlated negatively with its expression and lower EMP3 expression predicted better prognosis in LGGs patients.…”

Section: Discussionsupporting

confidence: 80%

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

Zeng

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the current study, we performed an integrated analysis of genome-wide methylation and gene expression data to find novel prognostic genes for lower-grade gliomas (LGGs). Methods: First, TCGA methylation data were used to identify prognostic genes associated with promoter methylation. Second, candidate genes that were stably regulated by promoter methylation were explored. Third, Cox proportional hazards regression analysis was used to generate a prognostic signature, and the signature genes were used to construct a survival risk score system. Results: Three genes (EMP3, GSX2 and EMILIN3) were selected as signature genes. These three signature genes were used to construct a survival risk score system. The high-risk group exhibited significantly worse overall survival (OS) and relapse-free survival (RFS) as compared to the low-risk group in the TCGA dataset. The association of the three-gene prognostic signature with patient’ survival was then validated using the CGGA dataset. Moreover, Kaplan-Meier plots showed that the three-gene prognostic signature risk remarkably stratified grade II and grade III patients in terms of both OS and RFS in the TCGA cohort. There was also a significant difference between the low- and high-risk groups in IDH wild-type glioma patients, indicating that the three-gene signature may be able to help in predicting prognosis for patients with IDH wild-type gliomas. Conclusion: We identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in LGGs by integrating multidimensional genomic data from the TCGA and CGGA datasets, which may help in fine-tuning the current histology-based tumors classification system and providing better stratification for future clinical trials.

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Section: Discussionsupporting

confidence: 80%

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

Zeng

Liu

et al. 2018

Cell Physiol Biochem

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“…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%

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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“…Therefore, it has a high degree of malignancy and poor prognosis (1). In addition, according to the World Health Organization (WHO) glioma grading criteria, gliomas can be classified as low-grade (WHO I-II) and high-grade (WHO III-IV) according to their degree of malignancy (2). Despite considerable advances in surgical resection (or a biopsy if surgery cannot be performed), radiotherapy and chemotherapy, the prognosis for glioma has not significantly improved (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, according to the World Health Organization (WHO) glioma grading criteria, gliomas can be classified as low-grade (WHO I-II) and high-grade (WHO III-IV) according to their degree of malignancy (2). Despite considerable advances in surgical resection (or a biopsy if surgery cannot be performed), radiotherapy and chemotherapy, the prognosis for glioma has not significantly improved (2,3). Median survival time of patients with glioblastoma multiforme, the most common and malignant type of glioma, is only 14.6 months, and the 5-year survival rate is less than 10% (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of collagen α‑1(III) inhibits glioma cell proliferation and migration and is regulated by miR128‑3p

et al. 2018

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As a member of the collagen family, collagen α-1(III) (COL3A1) is an important protein in the development and progression of several tumors. However, the role of COL3A1 in glioma is not yet clear. The present study examined the expression and function of COL3A1 in glioma cell behavior and identified microRNA (miRNA) regulators. It was demonstrated that COL3A1 expression was upregulated in glioma and directly correlated with the tumor grade. Analysis of the GSE4290 and GSE7696 profiles acquired from the Gene Expression Omnibus database also revealed an increased COL3A1 expression in malignant gliomas compared with the lower grade gliomas and non-tumor brain tissue, which was directly correlated with glioma grade. To explore the functional role of COL3A1 in glioma cell growth, small interfering RNA interference was applied to inhibit COL3A1 expression in Hs683 and U251 cells. The relative COL3A1 mRNA and protein expression levels were significantly reduced in the knockdown cells as determined by western blot analysis. In addition, decreased COL3A1 expression in Hs683 and U251 glioma cells resulted in a delay in cell growth and colony disruption as determined by MTS and colony formation assays. Wound healing analysis indicated that cells with suppressed expression of COL3A1 had a reduced ability to migrate. COL3A1 mRNA levels were inversely correlated with the miR128-3p level in glioma, suggesting that miR128-3p expression is associated with COL3A1 inhibition as verified by reverse transcription-quantified polymerase chain reaction. These results suggest that COL3A1 may be a novel regulator of glioblastoma cell behavior and may represent a novel target for gene therapies against glioma.

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PPIC, EMP3 and CHI3L1 Are Novel Prognostic Markers for High Grade Glioma

Cited by 45 publications

References 40 publications

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

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

Knockdown of collagen α‑1(III) inhibits glioma cell proliferation and migration and is regulated by miR128‑3p

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