Epigenetic silencing of KAZALD1 confers a better prognosis and is associated with malignant transformation/progression in glioma

WANG, HONGJUN; Feng, Ying; Bao, Zhaoshi; Yan, Wei; Wang, Yongzhi; ZHANG, CHUANBAO; LIU, YANWEI; Zhang, Quan-geng; Zhang, Wei; Jiang, Chuanlu

doi:10.3892/or.2013.2706

Cited by 18 publications

(17 citation statements)

References 22 publications

(25 reference statements)

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“…The scores were determined by combining the proportion of positively stained tumor cells and the intensity of staining. Binary decision criterion of Rab27b expression was performed as previously described (8,16).…”

Section: Bisulfite Sequencing Pcr (Bsp)mentioning

confidence: 99%

“…The cells were maintained in Dulbecco's modified Eagle's medium (DMEM; Gibco, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (FBS) and incubated at 37˚C in 5% CO 2 . Upon 80% confluency, the cells were starved in DMEM with 1% FBS for 24 h and maintained in this low serum condition for the course of treatment (8).…”

Section: Bisulfite Sequencing Pcr (Bsp)mentioning

confidence: 99%

“…To date, research has discovered many epigenetic mechanisms, for example promoter hypermethylation/hypomethylation, histone modifications, or non-coding RNA expression (5). Moreover, DNA methylation is typically a more stable and inheritable epigenetic pattern, and is an important hallmark of tumor development and progression (6)(7)(8). Although the important role of hypermethylation in the silencing of tumor-suppressor genes is now well-documented (9), a decrease in the level of methylation also contributes to numerous types of human cancer (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Hypomethylated Rab27b is a progression-associated prognostic biomarker of glioma regulating MMP-9 to promote invasion

Wang

Bao

et al. 2015

Oncology Reports

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In the present study, in order to analyze abnormalities in DNA methylation in glioma, we utilized a large cohort methylation microarray (119 glioma samples). Genes associated with tumor grade progression were screened through Significance Analysis of Microarrays (SAM) in the methylation microarray. We found that Rab27b was hypomethylated in high-grade glioma (anaplastic gliomas and glioblastomas) compared with low-grade glioma (astrocytoma, oligodendrocytoma and oligoastrocytoma) (p=0.02). In 52 glioma samples, we determined both the methylation status of the Rab27b promoter region and protein expression, and confirmed a negative correlation between the methylation status and expression (p<0.01). Immunohistochemistry of 91 gliomas revealed that the Rab27b expression scores of high-grade glioma were higher than scores of low-grade gliomas (p<0.01). In high‑grade gliomas, patients haboring Rab27b hypomethylation or overexpression had unfavorable survival prognosis. Transwell invasion assays identified that invasive cell number of glioma U87 and LN229 cells decreased when Rab27b was knocked down. Decreased invasion partly resulted from reduced expression and activation of MMP-9 after Rab27b knockdown. Downregulation of Rab27b also suppressed tumor growth in vivo. Hypomethylated Rab27b was identified as a progression-associated and prognostic molecular marker of glioma.

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Section: Bisulfite Sequencing Pcr (Bsp)mentioning

confidence: 99%

Section: Bisulfite Sequencing Pcr (Bsp)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypomethylated Rab27b is a progression-associated prognostic biomarker of glioma regulating MMP-9 to promote invasion

Wang

Bao

et al. 2015

Oncology Reports

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“…these results further confirm that methylation of sites in this region play a significant role in the malignant transformation of ovarian EM. Hypermethylation of promoter CpG islands in tumor suppressors is known to be a frequent, early reversible event in carcinogenesis and can contribute to disease progression (27). Although the frequency of RUNX3 methylation increased with pathological stage, there was no significant correlation with histological type, demonstrating that methylation may play a role in both the occurrence and development of EAOC regardless of histology.…”

Section: Discussionmentioning

confidence: 98%

RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis

et al. 2014

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Abstract. The aim of the present study was to investigate the role of epigenetic inactivation of the runt-related transcription factor 3 gene (RUNX3) in the malignant transformation of ovarian endometriosis. Samples obtained by microdissection and scraping included 30 malignant ovarian endometriotic cyst tissues and 30 corresponding eutopic endometrium tissues from the endometriosis-associated ovarian carcinoma (EAOC) group, 19 benign ovarian endometriotic cyst tissues and 22 corresponding eutopic endometrium tissues from the endometriosis (EM) group and 22 normal eutopic endometrium tissues from the control endometrium (CE) group. RUNX3 methylation status was determined by methylationspecific PCR and bisulfite sequencing, while levels of RUNX3 and ERα protein expression were evaluated using immunohistochemistry. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the malignant ovarian endometriotic cysts from the EAOC group was significantly higher than that in the benign ovarian endometriotic cysts from the EM group. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the eutopic endometrium from the EAOC group was significantly higher than that in the EM and CE groups. An inverse correlation between positive RUNX3 protein expression and methylation was observed and a positive correlation was shown between RUNX3 methylation and ERα protein expression. In the malignant ovarian endometriotic cysts from the EAOC group, there was no significant correlation between methylation frequency of the RUNX3 gene and histological type. However, the percentage of RUNX3 gene methylation was significantly higher in the tissue samples from patients with surgical stage IC EAOC than the percentage in patients with stage IA and IB disease. These results suggest that RUNX3 inactivation by promoter hypermethylation plays a role in the progression of malignant transformation of ovarian EM and is closely related to estrogen metabolism. Negative protein expression and abnormal RUNX3 methylation in the eutopic endometrium could be used as diagnostic markers in patients with ovarian EM who may be at an increased risk of developing EAOC.

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“…The mRNA expression levels of the hub genes between oligodendroglial tumor tissues and normal controls were analyzed using the ONCOMINE (http://www.oncomine.org) database [19], and the data were collected from three literatures [20][21][22]. Terms with a similarity > 0.3 are connected by edges.…”

Section: Expression Analysismentioning

confidence: 99%

Screening and Authentication of Key Genes and Prognostic Value Analysis in Oligodendroglial Tumors

Bao

Peng

2020

Preprint

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Background: Emerging evidence indicates that various functional genes with altered expression are involved in the human tumor progression. This study is aimed at identifying novel key genes that may be used for oligodendroglial tumor diagnosis, prognosis, and targeted therapy. Methods: This study included three expression proﬁles (GSE15824, GSE29796 and GSE108474) obtained from the Gene Expression Omnibus (GEO). GEO2R was used to analyze the diﬀerentially expressed genes (DEGs) between normal samples and oligodendroglial tumor, including oligodendroglioma and anaplastic oligodendroglioma. The functional and pathway enrichment analysis was performed by the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the identiﬁed DEGs was constructed using the Search Tool for the Retrieval of Interacting Gene, and hub genes were identiﬁed. ONCOMINE and The Cancer Genome Atlas (TCGA) databases were used to verify the expression of the hub genes in oligodendroglial tumor tissues and the hub genes on the overall survival of oligodendroglial tumor patients. Results: A total of 128 DEGs were identiﬁed from the three expression proﬁles. These DEGs were enriched with functional processes and pathways related to oligodendroglial tumor pathogenesis. From the PPI network, five hub genes were identiﬁed. The expression of the five hub genes was all upregulated in oligodendroglial tumor tissues compared with the control tissues. Kaplan-Meier survival curves indicated that high expression of cullin 3 (CUL3), cop9 signalosome subunit 8 (COPS8), cullin associated and neddylation dissociated 1 (CAND1), F-box protein 22 (FBXO22), and leucine rich repeat containing 41 (LRRC41) predicted poor overall survival in oligodendroglial tumor patients (all log-rank P < 0.01). Conclusions: These results revealed that the DEGs may serve as candidate key genes during oligodendroglial tumor pathogenesis. The five hub genes, including CUL3, COPS8, CAND1, FBXO22, and LRRC41, may serve as promising prognostic biomarkers in oligodendroglial tumor.

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Epigenetic silencing of KAZALD1 confers a better prognosis and is associated with malignant transformation/progression in glioma

Cited by 18 publications

References 22 publications

Hypomethylated Rab27b is a progression-associated prognostic biomarker of glioma regulating MMP-9 to promote invasion

Hypomethylated Rab27b is a progression-associated prognostic biomarker of glioma regulating MMP-9 to promote invasion

RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis

Screening and Authentication of Key Genes and Prognostic Value Analysis in Oligodendroglial Tumors

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