Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis.
Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis.
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整合染色体畸变和基因表达谱以剖析直肠肿瘤发生。
DOI：
10.1186/1471-2407-8-314
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发表时间：
2008-10-29
期刊：
影响因子：
3.8
通讯作者：
Morreau, Hans
中科院分区：
文献类型：
--
作者：
Lips, Esther H.;van Eijk, Ronald;de Graaf, Eelco J. R.;Oosting, Jan;de Miranda, Noel F. C. C.;Karsten, Tom;de Velde, Cornelis J. van;Eilers, Paul H. C.;Tollenaar, Rob A. E. M.;van Wezel, Tom;Morreau, Hans
直肠肿瘤的准确分期对于做出正确的治疗选择至关重要。在以前的研究中，我们发现17 p、18 q的缺失和8 q、13 q、20 q的增加可以区分腺瘤和癌组织，而1 q的增加与淋巴结转移有关。为了找到肿瘤分期的标志物，我们在这些特定染色体上寻找候选基因。我们对79例直肠肿瘤进行了基因表达微阵列分析，并将这些数据与来自同一样本系列的基因组数据相结合。我们进行了监督分析，以找到受影响的染色体上的候选基因，并验证了qRT-PCR和免疫组化的结果。基因表达和染色体不稳定性数据的整合揭示了这两种数据类型之间的相似性。监督分析发现，在1 q增益的情况下，EFNA 1的上调，EFNA 1的表达与靶基因（VEGF）的表达相关。BOP 1基因参与核糖体生物合成，与染色体不稳定性有关，在8 q增加的病例中过表达。SMAD 2在18 q上表达下调最多，STMN 3和TGIF 2在20 q上表达上调最多。SMAD 4的免疫组化与SMAD 2基因表达和18 q丢失相关。在综合分析的基础上，本研究确定了一个众所周知的CRC基因（SMAD 2）和几个其他基因（EFNA 1，BOP 1，TGIF 2和STMN 3），可能可用于直肠癌的表征。
Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes. We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry. Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF). The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss. On basis of integrative analysis this study identified one well known CRC gene (SMAD2) and several other genes (EFNA1, BOP1, TGIF2 and STMN3) that possibly could be used for rectal cancer characterization.
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影响因子：
4.4
作者：
de Bruin EC;van de Pas S;Lips EH;van Eijk R;van der Zee MM;Lombaerts M;van Wezel T;Marijnen CA;van Krieken JH;Medema JP;van de Velde CJ;Eilers PH;Peltenburg LT
通讯作者：
Peltenburg LT
影响因子：
8
作者：
Alberici, P;Jagmohan-Changur, S;Fodde, R
通讯作者：
Fodde, R
影响因子：
4.7
作者：
Andersen, Claus Lindbjerg;Wiuf, Carsten;Orntoft, Torben Falck
通讯作者：
Orntoft, Torben Falck
影响因子：
3
作者：
BUESS, G;MENTGES, B;BECKER, HD
通讯作者：
BECKER, HD
影响因子：
64.5
作者：
Eppert, K;Scherer, SW;Attisano, L
通讯作者：
Attisano, L