Identification of the Molecular Mechanisms for Dedifferentiation at the Invasion Front of Colorectal Cancer by a Gene Expression Analysis
Identification of the Molecular Mechanisms for Dedifferentiation at the Invasion Front of Colorectal Cancer by a Gene Expression Analysis
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DOI：
10.1158/1078-0432.ccr-08-0370
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发表时间：
2008-11
影响因子：
11.5
通讯作者：
Y. Oku;Takashi Shimoji;K. Takifuji;T. Hotta;S. Yokoyama;K. Matsuda;Takashi Higashiguchi;Toshiji Tominaga;T. Nasu;Koichi Tamura;Masaaki Matsuura;Satoshi Miyata;Yo Kato;Hiroki Yamaue;Yoshio Miki
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文献类型：
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作者：
Y. Oku;Takashi Shimoji;K. Takifuji;T. Hotta;S. Yokoyama;K. Matsuda;Takashi Higashiguchi;Toshiji Tominaga;T. Nasu;Koichi Tamura;Masaaki Matsuura;Satoshi Miyata;Yo Kato;Hiroki Yamaue;Yoshio Miki
目的：本研究的目的是确定结直肠癌癌症侵袭前沿伴随去分化的基因表达特征。实验设计：选择了两种类型的结直肠癌。两种类型均为浅表病变的高分化腺癌。一种类型在侵袭前沿显示去分化表型（A型，13个样本）；另一个显示在侵袭前沿几乎没有去分化的癌细胞（B型，12个样本）。激光显微切割与 cDNA 微阵列分析相结合，研究结直肠癌的浅表病变和侵袭前沿。结果：83个基因在A型和B型浅表病变中差异表达，并且根据这些基因将浅表病变样本正确分为两簇。有趣的是，入侵前沿的样本也被这些基因分成了两个相同的簇。文本挖掘方法选择了10个涉及导致癌细胞在侵袭前沿去分化的潜在机制的基因。潜在机制包括转化生长因子-β、Wnt 和 Hedgehog 信号网络。通过定量逆转录PCR计算10个基因的表达水平，确认8个基因在两种类型之间表达显着差异（P < 0.05）。 8 个基因的基因表达谱将 12 个测试用例分为两个簇，其中一个错误分类。结论：由来自转化生长因子-β、Wnt和Hedgehog信号三个网络的8个基因构建的分子机制被发现与结直肠癌侵袭前沿的去分化相关。
Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer. Experimental Design: Two types of colorectal cancer were selected. Both types were well-differentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (type A, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers. Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-β, Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification. Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-β, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.