Gene expression profile as a prognostic factor in high-grade gliomas

Czernicki, Tomasz; Żegarska, Jolanta; Pączek, L; Cukrowská, Božena; Grajkowska, Wiesława; Zajączkowska, A.; Brudzewski, K.; Ulaczyk, J.; Marchel, Andrzej

doi:10.3892/ijo.30.1.55

Cited by 13 publications

(13 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Survival-associated genes in gliomas have been reported in various studies (21)(22)(23)(24). Moreover, methylation microarray provides a more general, prognostic, genome-wide methylation profiling, which may have a role in individualized diagnosis and treatment.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis using methylation and gene expression microarrays reveals PDE4C as a prognostic biomarker in human glioma

et al. 2014

View full text Add to dashboard Cite

Abstract. Hypermethylation of tumor suppressor promoters is generally accepted to indicate poor prognosis in glioma; however, the DNA methylation patterns associated with different glioma prognoses remain to be elucidated. In the present study, promoter methylation and gene expression microarrays were used to screen candidate genes between different grades of glioma. Survival analysis was performed using the Kaplan-Meier (KM) method. Promoter methylation and protein expression of phosphodiesterase 4C (PDE4C) was examined in different grade gliomas and the correlation between PDE4C and wild-type (WT) p53 was evaluated in glioma cell lines. In addition, gene ontology and gene set variation analysis were used to examine PDE4C function. We found PDE4C exhibited promoter hypermethylation in high-grade glioma samples and hypomethylation in low-grade glioma, with PDE4C expression levels showing the reverse. This indicated PDE4C may be a candidate glioma biomarker. Through studies of PDE4C methylation and expression status in an independent cohort of 124 patient samples (56 low-grade and 63 high-grade glioma and 5 normal brain), we identified PDE4C as having significant promoter methylation and lower expression in high-grade glioma. Hypermethylation and reduced PDE4C protein expression were associated with grade progression and overall survival. In glioma cell lines, PDE4C was upregulated by demethylation treatment with 5-Aza-2'-deoxycytidine and WT p53 expression was downregulated after PDE4C siRNA suppression. Finally, we found PDE4C promoted apoptosis and inhibited migration in a U87 cell line. On the basis of these observations and the results from subset analysis, it is reasonable to conclude that PDE4C may function as a tumor suppressor by promoting apoptosis through the WT p53 pathway and inhibiting cell migration. The data show that PDE4C is downregulated through promoter hypermethylation in glioma.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated analysis using methylation and gene expression microarrays reveals PDE4C as a prognostic biomarker in human glioma

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Loss of chromosome 8p or downregulation of DLC1 expression has been associated with metastatic potential in various clones of liver or breast tumor cell lines as well as with reduced survival both of patients with high-grade gliomas and of hepatitis C virus-positive individuals with hepatocellular carcinoma awaiting liver transplantation. [24][25][26][27][28][29] The C4-2-B2 cell line, which metastasizes to bone, was isolated from LNCaP cells, which are androgen-dependent, nontumorigenic and nonmetastatic and possess one methylated DLC1 allele. 4,12 We have now shown that the amount of DLC1 mRNA in LNCaP cells is about five times that in C4-2-B2 cells.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated restoration of expression of the tumor suppressor gene DLC1 inhibits the proliferation and tumorigenicity of aggressive, androgen-independent human prostate cancer cell lines: prospects for gene therapy

et al. 2008

View full text Add to dashboard Cite

Our recent study showing highly recurrent loss of function of DLC1 (deleted in liver cancer 1), a tumor suppressor gene in primary prostate carcinoma (PCA), implicates this gene in the pathogenesis of this disease. To evaluate the response of PCA to oncosuppressive activity of DLC1, we examined now the effects of adenoviral vector for human DLC1 transduction into the DLC1-deficient, androgen-independent (AI) and aggressive human PCA cell lines PC-3 and C4-2-B2. Adenovirus-mediated restoration of DLC1 expression inhibited the proliferation, invasiveness and anchorage-independent growth of PC-3 and C4-2-B2 cells in vitro as well as the tumorigenicity of PC-3 cells in nude mice. It also induced cell-cycle arrest, inhibited the activation of RhoA and the formation of actin stress fibers. DLC1 induced apoptosis in C4-2-B2 cells, whereas it did not elicit such an effect in PC-3 cells. The abundance of the antiapoptotic protein Bcl-2 was greater in PC-3 cells than in C4-2-B2 cells, and PC-3 cells were rendered sensitive to DLC1-induced apoptosis by treatment with the Bcl-2 inhibitor HA14-1. These results suggest that adenovirus-mediated DLC1 transfer, alone or together with other agents, such as inhibitors of Bcl-2 or histone deacetylase, might prove effective in the treatment of aggressive, AI-PCA.

show abstract

“…Expression profi ling was able to identify specifi c subgroups within each disease that were associated with improved or decreased survival. Despite some prognostic value [ 35 ], the application in clinical practice has been limited due to a variety of reasons such as costs, equipment requirement, and the need of frozen material for good-quality whole genome expression profi le studies. Overall, as with all molecular tests in clinical practice, the use of FFPE-based assays is critical to the widescale acceptance of a biomarker due to the limited availability of fresh/frozen tissues.…”

Section: Expression Profi Lingmentioning

confidence: 99%

Molecular Pathology Techniques

Snuderl

2014

Molecular Pathology Library

View full text Add to dashboard Cite

Gene expression profile as a prognostic factor in high-grade gliomas

Abstract: Abstract. Some clinical factors have been useful in predicting prognosis in high-grade gliomas, however, unexpected differences in survival time have generated attempts to search for more precise parameters. It is clear that tumour behaviour depends mostly on gene alterations.

Cited by 13 publications

References 58 publications

Integrated analysis using methylation and gene expression microarrays reveals PDE4C as a prognostic biomarker in human glioma

Integrated analysis using methylation and gene expression microarrays reveals PDE4C as a prognostic biomarker in human glioma

Adenovirus-mediated restoration of expression of the tumor suppressor gene DLC1 inhibits the proliferation and tumorigenicity of aggressive, androgen-independent human prostate cancer cell lines: prospects for gene therapy

Molecular Pathology Techniques

Contact Info

Product

Resources

About