Minichromosome maintenance protein 7 in colorectal cancer: Implication of prognostic significance
Minichromosome maintenance protein 7 in colorectal cancer: Implication of prognostic significance
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DOI：
10.3892/ijo_00000003
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发表时间：
2008-08-01
影响因子：
5.2
通讯作者：
Ito, Hisao
中科院分区：
文献类型：
--
作者：
Nishihara, Keisuke;Shomort, Kohei;Ito, Hisao
微小染色体维持蛋白（MCM）是DNA复制的重要组成部分，也是多种人类肿瘤的预后标志物。MCM阳性但Ki 67阴性的细胞（例如原代卵母细胞）被认为是许可的非增殖群体，并且与一些人类肿瘤的临床病理学特征显著相关。在本研究中，我们评估了MCM 7，MCM 2和Ki 67在结直肠癌中的表达水平，以阐明其病理生物学意义。我们对5种人结直肠癌细胞系进行了Western印迹分析，并对202例Dukes' B和C期手术切除的结直肠癌进行了免疫组化。还对癌症标本进行了免疫荧光双标记，以鉴定MCM阳性但Ki 67阴性的肿瘤细胞。MCM蛋白在5种细胞系中均有表达。MCM 7和MCM 2在几乎相同的肿瘤细胞群中共表达，而在双标记的标本中，除了有丝分裂细胞外，不存在MCM 7阴性但Ki 67阳性的肿瘤细胞。MCM 7、MCM 2和Ki 67的平均阳性肿瘤标记指数（LI）分别为58.1%、57.1%和40.6%。MCM 7阳性但Ki 67阴性的肿瘤细胞的平均LI为17.6%，与N状态（P=0.01）、远处转移（P= 0.01）和ICC分期（P=0.02）显著相关。多因素考克斯回归分析显示，MCM 7高LI>58.1%是独立的预后因素（相对危险度= 2.12; P=0.02）。我们的研究结果表明，MCM 7的表达是一个独立的预后因素，人类结直肠癌，和MCM 7阳性，但Ki 67阴性的肿瘤细胞与肿瘤转移。
Minichromosome maintenance (MCM) proteins are essential components for DNA replication, and also prognostic markers for various human tumors. MCM-positive but Ki67-negative cells (e.g. primary oocytes) are thought to be licensed non-proliferating populations, and are significantly correlated with the clinicopathological profiles of some human tumors. In the present study, we evaluated the expression levels of MCM7, MCM2 and Ki67 in colorectal cancer to clarify their pathobiological significance. We carried out Western blot analyses of 5 human colorectal cancer cell lines and performed immunohistochemistry on 202 surgically removed colorectal cancers of Dukes' B and C stages. Double-labeling immunofluorescence was also carried out on the cancer specimens to identify MCM-positive but Ki67-negative tumor cells. MCM proteins were detected in all the 5 cell lines examined. MCM7 and MCM2 were coexpressed in almost the same populations of tumor cells, whereas MCM7-negative but Ki67-positive tumor cells were absent in the double-labeled specimens, except for mitotic cells. The mean positive tumor labeling indexes (LIs) for MCM7, MCM2 and Ki67 were 58.1, 57.1 and 40.6%, respectively. The mean LI for MCM7-positive but Ki67-negative tumor cells was 17.6%, and significantly correlated with the N status (P=0.01), distant metastasis (P=0.01) and UICC stage (P=0.02). The high LI of >58.1% for MCM7 were independent prognostic factors in multivariate Cox regression analysis (relative risk = 2.12; P=0.02). Our results indicate that MCM7 expression is an independent prognostic factor for human colorectal cancer, and MCM7-positive but Ki67-negative tumor cells are correlated with tumor metastases.