VEGF-D基因在肺腺癌、吉非替尼继发耐药肺腺癌及正常肺组织中的表达

VEGF-D expression in lung adenocarcinoma with or without acquired resistance to gefitinib and normal lung tissue

背景与目的表皮生长因子酪氨酸激酶受体抑制剂(epidermal growth factor receptor tyrosine inhibitor,EGFR-TKI)在治疗非小细胞肺癌中逐渐开始发挥重要作用,对EGFR-TKI继发耐药的机制亦日益受到关注。本研究旨在了解血管内皮生长因子D(vascular endothelial growth factor D,VEGF-D)基因在肺腺癌、吉非替尼继发耐药肺腺癌以及正常肺组织中的表达情况,以了解其在吉非替尼继发耐药中的作用。方法取外科切除的肺腺癌组织及癌旁正常肺组织、吉非替尼继发耐药肺腺癌组织(包括转移的淋巴结)。以β-actin为内参照,SYBR Green法实时定量PCR检测VEGF-D基因相对表达水平。确定阳性表达结果后,对表达率和表达水平进行定性和定量分析。结果对吉非替尼继发耐药肺腺癌(1/6,16.7%)、肺腺癌(7/14,50.0%)和正常肺组织(16/16,100.0%)中VEGF-D基因表达率用计算确切概率值法比较后,三组样本VEGF-D的表达率有显著差别(P=0.0000917)。7例VEGF-D基因表达阳性的肺癌组织VEGF-D表达水平经非参数检验显著低于对应的正常肺组织(P=0.000)。结论VEGF-D基因在正常肺组织中处于高表达状态,而在肺腺癌组织和吉非替尼继发耐药肺腺癌表达降低,说明其在肺癌及吉非替尼耐药肺癌组织所起的作用不同于正常肺组织。

Background and objective The epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) is playing an important role in the treatment of non-small cell lung cancer.The acquired resistance of EGFR-TKI has become a hot spot.This study aims to investigate VEGF-D expression level in lung adenocarcinoma with or without acquired resistance to gefitinib and in normal lung,so as to explore the role of VEGF-D in resistance of gefitinib.Methods Lung adenocarcinoma,normal lung tissues adjacent to the carcinoma and adenocarcinoma with acquired resistance to gefitinib including some metastastic lymph nodes were obtained during operation.SYBR Green real-time PCR with beta actin gene as the endogenous control was performed to examine VEGF-D gene expression semi-quantitatively.After positive expression of VEGF-D was determined,the expression ratio and level in each group was analyzed qualitatively and quantitatively.Results Exact significance was computed to compare VEGF-D expression ratios in groups of lung adenocarcinoma with acquired resistance to gefitinib(1/6,16.7%),lung adenocarcinoma(7/14,50.0%) and normal lung(16/16,100.0%) and the difference was significant(P=0.000 091 7).VEGF-D relative expression level in the seven lung adenocarcinoma cases was significantly lower than its corresponding normal lung tissue by analysis of nonparametric test(P<0.01).Conclusion VEGF-D has a high-level expression in normal lung tissues,while has a decreased expression in lung adenocarcinoma with or without acquired resistance to gefitinib,suggesting that VEGF-D functions in lung adenocarcinoma with or without acquired resistance to gefitinib in a way,which is different from in normal lung.