Molecular signature for lymphatic metastasis in colorectal carcinomas
Molecular signature for lymphatic metastasis in colorectal carcinomas
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DOI：
10.1097/sla.0b013e31816bcd49
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发表时间：
2008-05-01
影响因子：
9
通讯作者：
Lausen, Berthold
中科院分区：
文献类型：
--
作者：
Croner, Roland S.;Foertsch, Thomas;Lausen, Berthold
目的：结直肠癌的TNM分期依赖于手术切除标本的组织病理学检查。如果存在有效的术前分期方法，则可以选择患者在手术前进行适当的个体化治疗。微阵列技术提供了一个很有前途的工具，以确定特定阶段的分子签名上的原发性肿瘤biopsizes.Material和方法：40肿瘤样本的阶段UICC 1，11 CRC，40例III期CRC，和25活检的健康粘膜（MC）休克冷冻在液氮中，并进行冷冻后手动解剖肿瘤组织或MC富集。将分离的RNA与GeneChips（HG-U133 A，Affytechnology）杂交。微阵列结果的预处理通过稳健的多芯片平均方法进行，差异表达基因通过最大Wilcoxon统计在22，215个探针组中选择。结果进行了验证，在一个独立的临床研究。结果：50个不同的表达基因之间的阶段UICC 1，11与III CRC被确定尊重的选择标准，允许多次测试。独立临床研究的数据验证证实了我们的结果。与MC相比，这些基因被过度表达或表达不足。他们属于不同的功能组，如细胞粘附，转运，信号，代谢，蛋白质合成，基因控制，和免疫system.Conclusion：我们的大型患者队列和数据验证的一项独立的研究，确定了50个差异表达的基因之间的CRC的不同组织病理学阶段。这些研究结果表明，CRC的分子分期可能是可能的，这可能有助于指导手术前的个体CRC治疗。
Purpose: TNM-staging of colorectal carcinomas (CRC) relies on the histopathologic workup of the surgically removed specimen. If valid preoperative staging methods existed, patients could be selected for adequate individual therapy before surgery. Microarray techniques provide a promising tool to identify stage-specific molecular signatures on primary tumor biopsies.Material and Methods: Forty tumor samples of stage UICC 1, 11 CRC, 40 samples of stage III CRC, and 25 biopsies of healthy mucosa (MC) were shock frozen in liquid nitrogen and underwent cryotomy after manual dissection for tumor tissue or MC enrichment. Isolated RNA was hybridized to GeneChips (HG-U133A, Affymetrix). Preprocessing of the microarray results was done by the robust multichip average method, and differentially expressed genes were selected by the maximum Wilcoxon statistic over 22,215 probe sets. The results were validated at an independent clinical study.Results: Fifty differently expressed genes between stage UICC 1, 11 versus III CRC were identified respecting the selection criteria by allowing for multiple testing. The data validation by the independent clinical study confirmed our results. In comparison to MC, the genes were over- or underexpressed. They belong to various functional groups such as cellular adhesion, transporters, signaling, metabolism, protein synthesis, gene control, and immune system.Conclusion: Our large patient cohort and the data validation on an independent study identified 50 differentially expressed genes between CRC of different histopathologic stages. These findings indicate that molecular staging of CRC may be possible, which could help to guide individual CRC treatment before surgery.