单纯性肺泡癌和含有肺泡癌成分的腺癌基因差异比较

Differentially expressed genes between pure bronchioloalveolar carcinoma and pure bronchioloalve- olar carcinoma features by genechip

目的比较单纯性肺泡癌（PureBAC）与含有肺泡癌成分的腺癌（AWBF）的基因表达谱，研究与PureBAC进展相关的基因。方法选取PureBAC标本8例，以8例AWBF作对照。采用Agiilent 人4＊44Karrays全基因组芯片进行检测，应用DAVID、通路studi05．0、特征提取软件9．1等软件对基因芯片的结果进行统计学、聚类和差异表达分析。选取两组间差异表达的43个侵袭和转移的基因（P〈0．01），采用Real—time聚合酶链反应（PCR）验证基因芯片结果。应用SPSS统计软件分析。结果表达谱芯片共得到581个基因的有效数据，筛选出43个侵袭和转移的基因（P〈0．01），差异表达上调基因23个，下调基因20个。实时定量RT—PCR检测结果显示ATF-2基因的相对表达量单纯性BAC组明显高于AWBF组，而CLDN18基因在AWBF组明显增高（P〈0．01），而且CLDN18和AT2在BAC和AWBF中的基因表达差异倍数〉10倍。结论CLDN18和ATF2在BAC中和AWBF中基因表达有明显差异，两者的异常表达可能与单纯性BAC的进展有关。

Objective To investigate the genetic differences between pure bronchioloalveolar car- cinoma （BAC） and invasive mixed type adenocarcinoma with BAC features （AWBF） and to explore the molecular mechanism of pure BAC progression. Methods Total RNA was extract froml6 lung tissue speci- mens, ineludig 8 cases of BAC and 8 cases of AWBF. The BAC and AWBF were analyzed for gene expres- sion profiles using the Agiilent 4 ＊ 44K arrays. Differentially expressed candidate genes were validated u- sing quantitative real-time polymerase chain reaction （PCR）. The SPSS software was used for the analysis. Two-sided values of P were given, and statistical signifcance was set at P 〈 0. 01. Results We selected 43 genes correlated with tumor progression and metastasis. A total of 23 genes were significantly higher in the AWBF and 20 genes were lower. Of the 43 validated genes, CLDN18 and ATF-2 were found to have 〉 10 fold higher expression in AWBF （ P 〈 0. 01 ） than in BAC. Conclusion CLDN18 and ATF-2 may be related with the progression of BAC to AWBF. Furthermore, targeting these genes may be a promising way for AWBF treatment.