Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, Republic of China.
Clin Cancer Res. 2009 Dec 1;15(23):7309-15. doi: 10.1158/1078-0432.CCR-09-1572. Epub 2009 Nov 17.
Metastasis is the main cause of mortality in non-small cell lung cancer (NSCLC) patients. Genes that can discriminate the invasion ability of cancer cells may become useful candidates for clinical outcome prediction. We identify invasion-associated genes through computational and laboratorial approach that supported this idea in NSCLC.
We first conducted invasion assay to characterize the invasion abilities of NCI-60 lung cancer cell lines. We then systematically exploited NCI-60 microarray databases to identify invasion-associated genes that showed differential expression between the high and the low invasion cell line groups. Furthermore, using the microarray data of Duke lung cancer cohort (GSE 3141), invasion-associated genes with good survival prediction potentials were obtained. Finally, we validated the findings by conducting quantitative PCR assay on an in-house collected patient group (n = 69) and by using microarray data from two public western cohorts (n = 257 and 186).
The invasion-associated four-gene signature (ANKRD49, LPHN1, RABAC1, and EGLN2) had significant prediction in three validation cohorts (P = 0.0184, 0.002, and 0.017, log-rank test). Moreover, we showed that four-gene signature was an independent prognostic factor (hazard ratio, 2.354, 1.480, and 1.670; P = 0.028, 0.014, and 0.033), independent of other clinical covariates, such as age, gender, and stage.
The invasion-associated four-gene signature derived from NCI-60 lung cancer cell lines had good survival prediction power for NSCLC patients.
转移是导致非小细胞肺癌（NSCLC）患者死亡的主要原因。能够区分癌细胞侵袭能力的基因可能成为临床预后预测的有用候选基因。我们通过计算和实验室方法识别与侵袭相关的基因，为这一观点提供了支持。
我们首先进行侵袭实验，以确定 NCI-60 肺癌细胞系的侵袭能力。然后，我们系统地利用 NCI-60 微阵列数据库，鉴定出在高侵袭和低侵袭细胞系组之间表达差异的侵袭相关基因。此外，利用杜克肺癌队列（GSE3141）的微阵列数据，获得具有良好生存预测潜力的侵袭相关基因。最后，我们通过对内部收集的患者组（n=69）进行定量 PCR 检测，并使用来自两个西方公共队列（n=257 和 186）的微阵列数据，验证了这些发现。
侵袭相关的四基因特征（ANKRD49、LPHN1、RABAC1 和 EGLN2）在三个验证队列中均具有显著的预测意义（P=0.0184、0.002 和 0.017，对数秩检验）。此外，我们表明四基因特征是一个独立的预后因素（危险比分别为 2.354、1.480 和 1.670；P=0.028、0.014 和 0.033），独立于其他临床协变量，如年龄、性别和分期。
源自 NCI-60 肺癌细胞系的侵袭相关四基因特征对 NSCLC 患者具有良好的生存预测能力。
