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原发性口腔鳞状细胞癌中差异启动子高甲基化基因的筛选

Screening of differential promoter hypermethylated genes in primary oral squamous cell carcinoma.

作者信息

Khor Goot Heah, Froemming Gabrielle Ruth Anisah, Zain Rosnah Binti, Abraham Mannil Thomas, Thong Kwai Lin

机构信息

Centre of Preclinical Science Studies, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(20):8957-61. doi: 10.7314/apjcp.2014.15.20.8957.

Abstract

BACKGROUND

Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC).

OBJECTIVES

To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR).

MATERIALS AND METHODS

Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis.

RESULTS

TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status.

CONCLUSIONS

Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

摘要

背景

启动子高甲基化会导致基因功能改变,并可能导致细胞恶性转化。因此,鉴定高甲基化基因的生物标志物可能有助于口腔鳞状细胞癌(OSCC)的诊断、预后评估和治疗。

目的

用微阵列方法筛选高甲基化基因,并用甲基化特异性聚合酶链反应(MSPCR)验证所选的高甲基化基因。

材料与方法

使用Illumina甲基化微阵列对正常口腔黏膜和OSCC组织进行全基因组分析。选择特定的差异基因,并通过OSCC样本的独立队列样本进一步验证高甲基化状态。使用微阵列分析筛选候选基因,并通过MSPCR分析进行检测。

结果

TP73、PIK3R5和CELSR3表现出较高比例的差异高甲基化状态。

结论

我们的微阵列筛选和MSPCR方法表明,差异高甲基化基因的标志性候选基因可能成为潜在的生物标志物,在不久的将来可用于OSCC的诊断、预后评估和治疗靶点。

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