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ORAOV1 在口腔鳞状细胞癌中被扩增。

ORAOV1 is amplified in oral squamous cell carcinoma.

机构信息

Departmento de Patologia Bucal, Faculdade de Odontologia, Universidade de São Paulo, São Paulo, Brazil.

出版信息

J Oral Pathol Med. 2012 Jan;41(1):54-60. doi: 10.1111/j.1600-0714.2011.01053.x. Epub 2011 May 28.

Abstract

BACKGROUND

Oral cancer overexpressed 1 (ORAOV1) was found as a candidate oncogene in the 11q13 chromosomal region, based on its amplification and overexpression in oral cancer cell lines. Because gene amplification often leads to increased levels of gene expression, we aimed to verify the relationship between ORAOV1 gene status and mRNA expression primarily in oral squamous cell carcinoma (OSCC) by quantitative assay, correlating with clinical and pathological characteristics in patients.

METHODS

Levels of ORAOV1 amplification and expression were evaluated by qPCR and RT-qPCR in OSCC cell lines and in tumor and non-tumoral surgical margins from 33 patients with OSCC. All subjects were smokers and habitual alcohol drinkers, mostly men above 40 years of age and with a single primary tumor.

RESULTS

ORAOV1 exhibited increased gene expression levels as well as higher copy number in three OSCC cell lines with 11q13 amplified chromosomal region when compared with the OSCC cell line without the amplification (one-way ANOVA, P < 0.05). Weak correlation between ORAOV1 mRNA levels and DNA copy number was seen in tumor samples (Spearman, P = 0.07). Although ORAOV1 was amplified in tumor (Wilcoxon, P < 0.01), high levels of transcripts in margin did not reveal differences in comparison with tumor (Wilcoxon, P = 0.85). Aggressiveness and survival rate did not demonstrate statistical difference for both events in OSCC.

CONCLUSION

The overexpression of ORAOV1 in non-tumoral margin samples can occur in the absence of amplification. The weak correlation between ORAOV1 amplification and expression in OSSC suggests that ORAOV1 expression can be regulated by mechanisms other than gene amplification.

摘要

背景

基于其在口腔癌细胞系中的扩增和过表达,在 11q13 染色体区域发现口腔癌过表达 1(ORAOV1)是候选癌基因。由于基因扩增通常会导致基因表达水平升高,我们旨在通过定量检测主要在口腔鳞状细胞癌(OSCC)中验证 ORAOV1 基因状态与 mRNA 表达之间的关系,并与患者的临床和病理特征相关联。

方法

在 33 例 OSCC 患者的 OSCC 细胞系和肿瘤及非肿瘤手术切缘中,通过 qPCR 和 RT-qPCR 评估 ORAOV1 扩增和表达水平。所有患者均为吸烟者和习惯性饮酒者,主要为 40 岁以上的男性,且为单发原发性肿瘤。

结果

与未扩增的 OSCC 细胞系相比,三个具有 11q13 扩增染色体区域的 OSCC 细胞系中 ORAOV1 基因表达水平升高,且拷贝数更高(单因素方差分析,P<0.05)。肿瘤样本中 ORAOV1 mRNA 水平与 DNA 拷贝数之间呈弱相关性(Spearman,P=0.07)。尽管肿瘤中 ORAOV1 扩增(Wilcoxon,P<0.01),但与肿瘤相比,边缘高转录物水平没有差异(Wilcoxon,P=0.85)。OSCC 中两种情况的侵袭性和生存率均无统计学差异。

结论

在不存在扩增的情况下,非肿瘤边缘样本中 ORAOV1 的过表达可能发生。OSSC 中 ORAOV1 扩增与表达之间的弱相关性表明,ORAOV1 表达可以通过除基因扩增以外的机制进行调控。

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