MicroRNAs Potentially Important in Lung Cancer: P2-002
MicroRNAs Potentially Important in Lung Cancer: P2-002
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DOI：
10.1097/01.jto.0000283465.52560.17
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发表时间：
2007-08
影响因子：
20.4
通讯作者：
Morgan R. Davidson;Jill E. Larsen;R. Bowman;K. Fong
中科院分区：
文献类型：
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作者：
Morgan R. Davidson;Jill E. Larsen;R. Bowman;K. Fong
非小细胞肺癌（NSCLC）中血管内皮生长因子A（VEGF-A）表达增加和对血管生成抑制剂厄洛替尼的反应是否是一种新的预测标志物？Brueckl，Wolfgang M.1维尔茨，Ralph M.2 Schoeberl，Anja 1 Murray，Samuel 3 Hahn，Eckhart G.1 Wiest，Gunther H.1 1医学部1大学医院埃尔兰根，埃尔兰根，德国2西门子医疗解决方案，勒沃库森，德国3分子生物学部大都会医院，雅典，希腊背景：非小细胞肺癌（Non-small-cell lung cancer，NSCLC）是世界上最常见的恶性肿瘤，预后差。最近，埃罗替尼，一种上皮生长因子受体（EGF-R）酪氨酸激酶抑制剂已被证明是有效的二线/三线化疗的生存。然而，总体答复率约为9%。EGF-R基因的体细胞突变或EGF-R基因的扩增似乎与对厄洛替尼的应答相关。方法和结果：我们报告了一位年轻的不吸烟的白人女性非小细胞肺癌患者，她在一线铂类药物联合治疗后病情进展。她对厄洛替尼作为二线治疗有良好的部分应答，持续时间超过6个月。通过对EGF-R基因和K-RAS基因的外显子19-21进行测序，在肿瘤或肝转移中没有检测到体细胞突变。此外，使用显色原位杂交（CiSH），在肿瘤或转移灶中没有发现EGF-R扩增。然而，我们发现VEGF-A mRNA在原发性肺肿瘤和肝转移瘤中过表达，与正常肺上皮相比。免疫组化证实VEGF-A在蛋白质水平过度表达。结论：这些发现有助于假设，EGF-R和VEGF途径之间可能存在关联。此外，VEGF表达可能是NSCLC对厄洛替尼治疗反应的另一个标志物。为了进一步分析这一潜在的预测因素，应系统研究厄洛替尼治疗应答者的VEGF表达。
Increased vascular-endothelial growth factor A (VEGF-A) expression and response to angiogenesis inhibitor erlotinib in non-small-cell lung cancer (NSCLC) Hint for a new predictive marker? Brueckl, Wolfgang M.1 Wirtz, Ralph M.2 Schoeberl, Anja1 Murray, Samuel3 Hahn, Eckhart G.1 Wiest, Gunther H.1 1 Dept of Medicine 1 University Hospital Erlangen, Erlangen, Germany 2 Siemens Medical Solutions, Leverkusen, Germany 3 Dept of Molecular Biology Metropolitan Hospital, Athens, Greece Background: Non-small-cell lung cancer (NSCLC) is the most common cancer in the world and prognosis is poor. Recently, erlotinib, an epithelial growth factor receptor (EGF-R) tyrosine kinase inhibitor has shown to be effective in terms of survival in second/third-line chemotherapy. However, the overall response rate is about 9%. Somatic mutations of the EGF-R gene or amplifications of the EGF-R gene seem to be associated with response to erlotinib. Methods and Results: We report about a young non-smoking Caucasian woman with metastastic NSCLC progressive to first-line platinbased combination therapy. She had a good partial response to erlotinb as second line therapy lasting over 6 months. By sequencing exons 19-21 of the EGF-R gene and the K-RAS gene, there was no somatic mutation detectable in the tumour or in a liver metastasis. Additionally, using chromogenic in situ Hybridisation (CiSH) there was no EGF-R amplification found in the tumour or metastasis. However, we found a VEGF-A mRNA overexpression in the primary lung tumour and liver metastasis in comparisson to normal lung epithilium. VEGF-A overexpression was confirmed at the protein level by immunohistochemistry. Conclusions: These findings contribute to the hypothesis, that there might be an association between the EGF-R and VEGF pathways. Furthermore, VEGF expression might be another marker for response to erlotinib therapy in NSCLC. To further analyse this potential predictive factor, VEGF expression should be studied systematically in responders to erlotinib therapy.