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首页> 外文期刊>Annals of oncology: official journal of the European Society for Medical Oncology >EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines.
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EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines.

机译：microRNA在肺癌中对EGFR的调节：与吉非替尼和细胞系中gefitinib和EGFR表达的临床反应及生存相关。

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BACKGROUND: Allelic loss in chromosome 3p is one of the most frequent and earliest genetic events in lung carcinogenesis. We investigated if the loss of microRNA-128b, a microRNA located on chromosome 3p and a putative regulator of epidermal growth factor receptor (EGFR), correlated with response to targeted EGFR inhibition. Loss of microRNA-128b would be equivalent to losing a tumor suppressor gene because it would allow increased expression of EGFR. PATIENTS AND METHODS: We initially showed that microRNA-128b is a regulator of EGFR in non-small-cell lung cancer (NSCLC) cell lines. We tested microRNA-128b expression levels by quantitative RT-PCR, genomic copy number by quantitative PCR, and mutations in the mature microRNA-128b by sequencing. We determined whether microRNA-128b loss of heterozygosity (LOH) in 58 NSCLC patient samples correlated with response to gefitinib and evaluated EGFR expression and mutation status. RESULTS: We determined that microRNA-128b directly regulates EGFR. MicroRNA-128b LOH was frequent in tumor samples and correlated significantly with clinical response and survival following gefitinib. EGFR expression and mutation status did not correlate with survival outcome. CONCLUSION: Identifying microRNA regulators of oncogenes could have far-reaching implications for lung cancer patients including improving patient selection for targeted agents, development of novel therapeutics, or development as early biomarkers of disease.
机译：背景：3p染色体的等位基因缺失是肺癌致癌中最常见，最早的遗传事件之一。我们调查了microRNA-128b，位于3p染色体上的microRNA和表皮生长因子受体（EGFR）的假定调节物的丢失是否与对靶向EGFR抑制的反应相关。 microRNA-128b的丢失将等同于肿瘤抑制基因的丢失，因为它可以增加EGFR的表达。患者和方法：我们最初显示microRNA-128b是非小细胞肺癌（NSCLC）细胞系中EGFR的调节剂。我们通过定量RT-PCR测试了microRNA-128b的表达水平，通过定量PCR测试了基因组拷贝数，并通过测序测试了成熟的microRNA-128b的突变。我们确定了58例NSCLC患者样品中的microRNA-128b杂合性缺失（LOH）是否与对吉非替尼的反应相关，并评估了EGFR表达和突变状态。结果：我们确定microRNA-128b直接调节EGFR。 MicroRNA-128b LOH在肿瘤样品中很常见，并且与吉非替尼治疗后的临床反应和生存率显着相关。 EGFR的表达和突变状态与生存结果无关。结论：鉴定癌基因的微RNA调节剂可能对肺癌患者具有深远的影响，包括改善患者对靶向药物的选择，开发新疗法或发展为疾病的早期生物标记。

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