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DACT1和DACT2在口腔鳞状细胞癌中的表达及表观遗传调控

Expression and epigenetic regulation of DACT1 and DACT2 in oral squamous cell carcinoma.

作者信息

Schussel Juliana Lucena, Kalinke Luciana Puchalski, Sassi Laurindo Moacir, de Oliveira Benedito Valdecir, Pedruzzi Paola A G, Olandoski Marcia, Alvares Lucia Elvira, Garlet Gustavo Pompermaier, Trevilatto Paula Cristina

机构信息

School of Health and Biosciences, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil Department of Oral and Maxillofacial Surgery, Erasto Gaertner Cancer Hospital, Curitiba, Brazil.

School of Health and Biosciences, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

出版信息

Cancer Biomark. 2015;15(1):11-7. doi: 10.3233/CBM-140436.

DOI:10.3233/CBM-140436
PMID:25524937
Abstract

BACKGROUND

DACT genes regulates Wnt as well TGF-β pathway, and were already associated with hepatocellular and lung cancer. Alterations on Wnt/β-catenin were associated with head and neck cancer through β-catenin cytoplasmatic accumulation.

OBJECTIVE

The aim of the study was to evaluate DACT1 and DACT2 expression and methylation on oral squamous cell cancer (OSCC).

METHODS

47 samples of salivary rinse and tissue were collected from 29 OSCC and 18 control patients. qMSP and RT-PCR reactions were performed in order to detect hypermethylation and expression of DACT1 and DACT2 genes. Statistical analysis was conducted to evaluate these genes as possible biomarkers for OSCC.

RESULTS

As expected man over 60 years old with tobacco and alcohol consumption history were associated with OSCC. There was no statistical difference between groups concerning DACT1 and DACT2 either in promoter hypermethylation or transcript levels. Age was associated with DACT2 promoter hypermethylation, especially over 56 years old.

CONCLUSION

Patients older than 56 years old were about 5 times more likely to have DACT2 promoter hypermethylation. These findings could partially explain why older subjects are more prone to carcinogenesis. Wnt/β-catenin pathway plays an important role in carcinogenesis, and the study of their regulators may help understand malignant transformation.

摘要

背景

DACT基因调控Wnt以及TGF-β信号通路,并且已被证实与肝细胞癌和肺癌相关。Wnt/β-连环蛋白的改变通过β-连环蛋白在细胞质中的积累与头颈癌相关。

目的

本研究旨在评估DACT1和DACT2在口腔鳞状细胞癌(OSCC)中的表达及甲基化情况。

方法

从29例OSCC患者和18例对照患者中收集了47份漱口水样本和组织样本。进行qMSP和RT-PCR反应以检测DACT1和DACT2基因的高甲基化及表达情况。进行统计分析以评估这些基因作为OSCC潜在生物标志物的可能性。

结果

正如预期的那样,60岁以上有吸烟和饮酒史的男性与OSCC相关。在启动子高甲基化或转录水平方面,DACT1和DACT2在两组之间没有统计学差异。年龄与DACT2启动子高甲基化相关,尤其是56岁以上的人群。

结论

56岁以上的患者发生DACT2启动子高甲基化的可能性约为5倍。这些发现可以部分解释为什么老年受试者更容易发生癌变。Wnt/β-连环蛋白信号通路在致癌过程中起重要作用,对其调节因子的研究可能有助于理解恶性转化。

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