Expression profiling of microdissected matched prostate cancer samples reveals CD166/MEMD and CD24 as new prognostic markers for patient survival
Expression profiling of microdissected matched prostate cancer samples reveals CD166/MEMD and CD24 as new prognostic markers for patient survival
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DOI：
10.1002/path.1676
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发表时间：
2005-02-01
影响因子：
7.3
通讯作者：
Rosenthal, A
中科院分区：
文献类型：
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作者：
Kristiansen, G;Pilarsky, C;Rosenthal, A
为了筛选可能对前列腺癌诊断和治疗有用的差异表达基因，我们使用了一种定制的含有3950个cDNA片段的Affyssin基因芯片。从显微切割的恶性和良性前列腺组织中分离的42对匹配的mRNA获得表达谱。应用三种不同的生物信息学方法来定义差异基因表达，我们发现了277个差异表达的基因，其中98个被所有三种方法鉴定。这些基因中有14%在其他基于大块组织的表达研究中没有发现。通过定量RT-PCR、mRNA原位杂交和免疫组化进一步验证候选基因。AGR 2在89%的前列腺癌中过度表达，但没有预后意义。MEMD和CD 24的过度表达分别在86%和38.5%的前列腺癌中被确定，并且两者都是PSA复发的预测因子。在考克斯回归模型中，使用MEMD和CD 24表达的组合标记分析被证明是独立的预后因素（RR = 4.7，p = 0.006），并且也上级于常规标记。因此，这种分子标志物的组合似乎可以改善对患者预后的预测，但应在更大的研究中进行验证。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
In order to screen for differentially expressed genes that might be useful in diagnosis therapy of prostate cancer we have used a custom made Affymetrix GeneChip containing 3950 cDNA fragments. Expression profiles were obtained from 42 matched pairs of mRNAs isolated from microdissected malignant and benign prostate tissues. Applying three different bioinformatic approaches to define differential gene expression, we found 277 differentially expressed genes, of which 98 were identified by all three methods. Fourteen per cent of these genes were not found in other expression studies, which were based on bulk tissue. Resultant candidate genes were further validated by quantitative RT-PCR, mRNA in situ hybridization and immunohistochemistry. AGR2 was over-expressed in 89% of prostate carcinomas, but did not have prognostic significance. Immunohistologically detected overexpression of MEMD and CD24 was identified in 86% and 38.5% of prostate carcinomas respectively, and both were predictive of PSA relapse. Combined marker analysis using MEMD and CD24 expression proved to be an independent prognostic factor (RR = 4.7, p = 0.006) in a Cox regression model, and was also superior to conventional markers. This combination of molecular markers thus appears to allow improved prediction of patient prognosis, but should be validated in larger studies. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.