【摘要】 背景与目的:远处转移是肺癌患者的重要死因,癌转移可能与细胞内基因表达模式改变有关。急需运用新技术来筛选和分析这些基因,以便进一步阐明癌转移的机制并寻找新的治疗靶点。本研究旨在筛选肺腺癌患者淋巴转移差异表达基因。方法:原发癌组织及区域淋巴结取自22例接受根治性手术的肺腺癌患者。根据组织来源将标本分为三组:不伴淋巴转移的肺腺癌组织(TxN-,n=11)、伴有淋巴转移的肺腺癌组织(TxN+,n=11)及相应转移淋巴结中的肺腺癌细胞(N+,n=11)。对各组进行激光显微切割以获得纯净癌细胞,T7RNA线性扩增获取足够量的RNA,实验通道和参照通道分别标记以后与含6000个已知人类基因或表达序列标签的cDNA基因芯片杂交,扫描荧光信号以后进行数据分析。结果:TxN+组与TxN-组共有17个差异表达基因,其中12个基因表达上调,5个基因表达下调。有53个基因可将N+组与TxN+组区分开,其中在N+组高表达的基因有25个,在TxN+组高表达的有28个。结论:早期癌形成中的遗传学变化和后期癌进展中的获得性分子学变异共同决定肺腺癌的淋巴转移。更多还原

【Abstract】 Background and Objective:Distant metastasis is a major cause of mortality for patients with lung adenocarcinoma.So far,the mechanism of tumor metastasis is unknown.This study was to screen the gene expression signature in relation to lymphatic metastasis of human lung adenocarcinoma.Methods:Primary lung adenocarcinoma tissues and regional lymph nodes were obtained from 22 patients underwent radical resection.The samples were classified into three groups:11 cases of primary lung adenocarcinoma without lymphatic metastasis(TxN-),11 cases of primary lung adenocarcinoma with lymphatic metastasis(TxN+),and 11 cases of the corresponding tumor cells from metastatic lymph nodes(N+).Total RNA was extracted from laser microdissected tumor samples.Adequate RNA starting materials from the primary tumors or metastatic nodes were labeled and then hybridized into the same microarray containing 6000 known human genes or expressed sequence tags(ESTs).After scanning,data analyses were performed using GeneSpringTM 6.2.Results:Among 17 differentially expressed genes between the TxN + and TxN-groups,12 genes were significantly elevated and five genes were significantly downregulated in the TxN + group compared with the TxN-group.There were 53 differentially regulated genes between the N+ and TxN+ groups,among which 25 genes were overexpressed and 28 genes were suppressed in the N + group.Conclusion:The combination of early oncogenic alterations and later acquisition of a set of genetic alterations may determine the metastatic potential of lung adenocarcinoma.更多还原