Stav D, Bar I, Sandbank J
Pulmonary Institute, Assaf Harofeh Medical Center, Zerifin, Israel.
Int J Biol Markers. 2007 Apr-Jun;22(2):108-13. doi: 10.1177/172460080702200204.
We used oligonucleotide microarrays with probe sets to 22,283 genes to analyze the gene expression profile of lung adenocarcinoma. Cancerous and noncancerous tissue samples were obtained from 23 patients with stage I or II lung cancer; 18 tissue pairs and 5 cancerous tissues. A list of 2065 genes that differentiate between cancerous and noncancerous tissues was generated using Winsorized paired t-tests. We analyzed CDK5RAP3 and CCNB2, which are involved in cell cycle progression, and RAGE. The first 2 of these 3 genes proved to be overexpressed in tumor tissue, whereas the RAGE gene was suppressed in tumor tissue. When CDK5RAP3 and CCNB2 were examined in individual patients we found that in cases where one of these genes was only slightly overexpressed the other was highly overexpressed. The combined expression of the 2 cell cycle genes was found to be statistically significant for differentiating between cancerous and noncancerous tissues. Inclusion of the data for the RAGE gene made the differentiation more powerful. The gene expression ratio gave a clear result: when CDK5RAP3 was expressed more than RAGE, the tissue was carcinomatous, and vice versa. We therefore conclude that these 3 genes may be used as a very reliable biomarker of lung adenocarcinoma.
我们使用了带有针对22283个基因的探针集的寡核苷酸微阵列来分析肺腺癌的基因表达谱。从23例I期或II期肺癌患者中获取癌组织和非癌组织样本;18对组织和5个癌组织。使用温莎化配对t检验生成了一份区分癌组织和非癌组织的2065个基因的列表。我们分析了参与细胞周期进程的CDK5RAP3和CCNB2以及RAGE。这3个基因中的前两个在肿瘤组织中被证明过度表达,而RAGE基因在肿瘤组织中受到抑制。当对个体患者的CDK5RAP3和CCNB2进行检测时,我们发现其中一个基因仅轻微过度表达的情况下,另一个基因则高度过度表达。发现这两个细胞周期基因的联合表达对于区分癌组织和非癌组织具有统计学意义。纳入RAGE基因的数据使区分能力更强。基因表达比率给出了明确的结果:当CDK5RAP3的表达高于RAGE时,组织为癌组织,反之亦然。因此,我们得出结论,这3个基因可用作肺腺癌非常可靠的生物标志物。