Expression profiling of primary non-small cell lung cancer for target identification
Expression profiling of primary non-small cell lung cancer for target identification
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DOI：
10.1038/sj.onc.1205979
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发表时间：
2002-10-31
期刊：
影响因子：
8
通讯作者：
Rickert, P
中科院分区：
文献类型：
--
作者：
Heighway, J;Knapp, T;Rickert, P
使用包括47 650个转录元件的cDNA微阵列面板，我们进行了双通道分析的基因表达在39个切除的原发性人非小细胞肺肿瘤与正常肺组织。虽然有11000个元素在至少一个样本中被评分为差异表达至少两倍，但在39个肿瘤中至少有7个中有96个转录本被评分为过度表达4倍或更多，在39个肿瘤中至少有2个中有30个序列被评分为过度表达16倍，其中包括24个共同的转录本。转录本（178）在39个肿瘤中的至少7个中被发现低于4倍，其中31个在39个病变中的至少2个中低于16倍。通过比较多重RT-PCR分析来自这些列表的代表性基因的相对表达水平，发现与微阵列数据大致一致。两个显著过度表达的基因，以前被指定为乳腺癌（maspin）和肺癌和乳腺癌（S100A2）的潜在肿瘤抑制因子，被更广泛地分析，并证明这种方法在识别潜在的肺癌诊断或治疗靶点方面的有效性。虽然已经报道了S100A2在NSCLC的早期阶段下调，但我们的微阵列、cmRT-PCR、Western和免疫组化数据表明，它在大多数肿瘤中强烈表达。
Using a panel of cDNA microarrays comprising 47 650 transcript elements, we have carried out a dual-channel analysis of gene expression in 39 resected primary human non-small cell lung tumours versus normal lung tissue. Whilst similar to11000 elements were scored as differentially expressed at least twofold in at least one sample, 96 transcripts were scored as over-represented fourfold or more in at least seven out of 39 tumours and 30 sequences 16-fold in at least two out of 39 tumours, including 24 transcripts in common. Transcripts (178) were found under-represented fourfold in at least seven out of 39 tumours, 31 of which are under-represented 16-fold in at least two out of 39 lesions. The relative expression levels of representative genes from these lists were analysed by comparative multiplex RT-PCR and found to be broadly consistent with the microarray data. Two dramatically over-represented genes, previously designated as potential tumour suppressors in breast (maspin) and lung and breast (S100A2) cancers, were analysed more extensively and demonstrate the effectiveness of this approach in identifying potential lung cancer diagnostic or therapeutic targets. Whilst it has been reported that S100A2 is downregulated in NSCLC at an early stage, our microarray, cmRT-PCR, Western and immunohistochemistry data indicate that it is strongly expressed in the majority of tumours.