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涎腺肿瘤中EGFR的表达、突变及扩增状态及其与五种miRNA的相关性

Expression, Mutation, and Amplification Status of EGFR and Its Correlation with Five miRNAs in Salivary Gland Tumours.

作者信息

Boštjančič Emanuela, Hauptman Nina, Grošelj Aleš, Glavač Damjan, Volavšek Metka

机构信息

Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Zaloška Cesta 4, 1000 Ljubljana, Slovenia.

Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Zaloška Cesta 2, 1000 Ljubljana, Slovenia.

出版信息

Biomed Res Int. 2017;2017:9150402. doi: 10.1155/2017/9150402. Epub 2017 Mar 9.

Abstract

Malignant salivary gland tumours are rare histologically and clinically heterogeneous group of tumours, missing prognostic factors and therapeutic targets. MicroRNAs (miRNAs), small noncoding RNAs, and posttranscriptional regulators of mRNA are poorly described in different subtypes of salivary gland tumours. Epidermal growth factor receptor (EGFR), an important therapeutic target and target of certain miRNAs (i.e., ), shows variable degrees of expression in salivary gland tumours. Our study included 70 parotid gland tumours of different histological subtypes. Expression, mutations, and copy number variations (CNVs) of EGFR were determined using immunohistochemistry, single-stranded conformation polymorphism, quantitative polymerase chain reaction (qPCR), and fluorescence in situ hybridization. Expression of , , , , and was analysed using qPCR. Expression of EGFR was observed in 37% of tumours with low and 40% of tumours with high malignant potential. There were no mutations, with the majority of samples showing polysomy of chromosome 7. Based on histological subtypes, we found differential expression of all five miRNAs. We confirmed association of reactivity of EGFR, , , , and with CNV of EGFR and a positive association between / and reactivity of EGFR. Age and need for postoperative radiotherapy were characterized as significant in multivariate survival analysis.

摘要

恶性唾液腺肿瘤在组织学上较为罕见,是一组临床异质性肿瘤,缺乏预后因素和治疗靶点。微小RNA(miRNA)是一类小的非编码RNA,作为mRNA的转录后调节因子,在唾液腺肿瘤的不同亚型中鲜有描述。表皮生长因子受体(EGFR)是一个重要的治疗靶点以及某些miRNA(如 )的作用靶点,在唾液腺肿瘤中呈现出不同程度的表达。我们的研究纳入了70例不同组织学亚型的腮腺肿瘤。采用免疫组织化学、单链构象多态性、定量聚合酶链反应(qPCR)和荧光原位杂交技术检测EGFR的表达、突变及拷贝数变异(CNV)。运用qPCR分析 、 、 、 和 的表达。在恶性潜能低的肿瘤中,37%观察到EGFR表达,在恶性潜能高的肿瘤中,40%观察到EGFR表达。未发现突变,大多数样本显示7号染色体多体性。基于组织学亚型,我们发现所有这五种miRNA均有差异表达。我们证实了EGFR、 、 、 和 的反应性与EGFR的CNV相关,且 / 与EGFR的反应性呈正相关。在多因素生存分析中,年龄和术后放疗需求具有显著意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/819a/5362712/0ac5e7786288/BMRI2017-9150402.001.jpg

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