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非小细胞肺癌中表皮生长因子受体(EGFR)信使核糖核酸(mRNA)表达水平升高

Increased EGFR mRNA Expression Levels in Non-Small Cell Lung Cancer.

作者信息

Tasdemir Sener, Taheri Serpil, Akalin Hilal, Kontas Olgun, Onal Omer, Ozkul Yusuf

机构信息

Department of Medical Genetics, Atatürk University School of Medicine, Erzurum, Turkey.

Department of Medical Biology, Erciyes University School of Medicine, Kayseri, Turkey.

出版信息

Eurasian J Med. 2019 Jun;51(2):177-185. doi: 10.5152/eurasianjmed.2016.0237. Epub 2017 Jan 25.

Abstract

OBJECTIVE

In this study, we investigated the frequency of Epidermal growth factor receptor (EGFR) gene mutations, the level of EGFR mRNA and protein expressions in Turkish population for indicating substantial differences in the frequency of EGFR mutations, EGFR amplification and EGFR protein expression between populations and the effect of these parameters in response to EGFR tyrosine kinase inhibitors.

MATERIALS AND METHODS

The study included 34 patients with non-small cell lung cancers. The RNA and DNA were extracted from the normal and tumor side of the lung tissue removed by surgery. To investigate the most common mutations in the EGFR gene, exon 19 was sequenced and mutation specific PCR was performed for detecting the L858R mutation in exon 21. EGFR mRNA expression was measured by relative quantitative reverse transcription PCR. The EGFR protein levels were detected with immunohistochemistry methods from the sections of the patients' paraffin blocks.

RESULTS

No EGFR mutation in exon 19 or L858R mutation in exon 21 were detected in the patients. Overexpression of EGFR gene mRNA was identified in 16 of 34 (%47) patients and overexpression of EGFR protein was detected in 15 of 34 (%44) patients. Statistical analysis was not significant for the correlation between sex, age, smoking, histopathology, pathological stage and overexpression of EGFR mRNA and protein.

CONCLUSION

It was found that in Turkish population, EGFR mutation in exon 19 and L858R mutation were very rare, EGFR protein expression was similar and EGFR mRNA expression significantly increased compared to the literature. Markedly increased EGFR mRNA expression ratios in the absence of activating mutations showed that identifying the EGFR mRNA expression level for prediction of response to EGFR tyrosine kinase inhibitors might be significant in the Turkish population.

摘要

目的

在本研究中,我们调查了土耳其人群中表皮生长因子受体(EGFR)基因突变的频率、EGFR mRNA和蛋白表达水平,以表明不同人群之间EGFR突变频率、EGFR扩增及EGFR蛋白表达的显著差异,以及这些参数对EGFR酪氨酸激酶抑制剂反应的影响。

材料与方法

该研究纳入了34例非小细胞肺癌患者。从手术切除的肺组织正常侧和肿瘤侧提取RNA和DNA。为研究EGFR基因中最常见的突变,对第19外显子进行测序,并进行突变特异性PCR以检测第21外显子中的L858R突变。通过相对定量逆转录PCR测量EGFR mRNA表达。用免疫组织化学方法从患者石蜡块切片中检测EGFR蛋白水平。

结果

患者中未检测到第19外显子的EGFR突变或第21外显子的L858R突变。34例患者中有16例(47%)检测到EGFR基因mRNA过表达,34例患者中有15例(44%)检测到EGFR蛋白过表达。性别、年龄、吸烟、组织病理学、病理分期与EGFR mRNA和蛋白过表达之间的相关性经统计学分析无显著意义。

结论

发现在土耳其人群中,第19外显子的EGFR突变和L858R突变非常罕见,EGFR蛋白表达相似,与文献相比EGFR mRNA表达显著增加。在无激活突变的情况下EGFR mRNA表达率明显增加,表明在土耳其人群中确定EGFR mRNA表达水平以预测对EGFR酪氨酸激酶抑制剂的反应可能具有重要意义。

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