A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer
A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer
复制标题
五基因特征作为结直肠癌转移和生存的潜在预测因子
DOI：
10.1002/path.2668
复制
发表时间：
2010-03-01
影响因子：
7.3
通讯作者：
Li, Jian-Ming
中科院分区：
文献类型：
--
作者：
Hao, Jun-Mei;Chen, Juan-Zhi;Li, Jian-Ming
为了了解结直肠癌（CRC）转移和预后的分子机制，我们在体外从SW 480细胞中分离出单细胞衍生的后代（SCP），并在体内原位CRC肿瘤模型中比较它们的转移潜力。获得了两组分别具有高转移能力和低转移能力的SCP。通过分析高（SCP 51），低（SCP 58）转移性SCP及其亲本细胞系（SW 480/EGFP）的基因表达谱，我们证明了143个基因在SCP 51和SCP 58之间或SCP 58和SW 480/EGFP之间差异表达。大卫的基因注释富集分析揭示了分析的前十个簇中的80个基因（基因富集得分>1）。在80个基因组中，32个基因可能参与转移，如Geneclip所揭示的。选择五个推定的转移基因（林恩、SDCBP、MAP 4K 4、DKK 1和MID 1）用于进一步验证。对181例CRC临床样本的免疫组化分析显示，林恩、MAP 4K 4和MID 1的个体表达以及5个基因标签与CRC患者的淋巴结转移密切相关。更重要的是，林恩、MAP 4K 4、SDCBP和MID 1的个体表达，以及5个基因标签，与CRC患者的总生存率显著相关。因此，我们的五基因签名可能能够预测临床上CRC的转移和生存，并为CRC的生物学开辟了新的视角。版权所有（C）2009大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell-derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene-annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score >1). Of the 80-gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five-gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five-gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five-gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.