A 'DNA replication' signature of progression and negative outcome in colorectal cancer
A 'DNA replication' signature of progression and negative outcome in colorectal cancer
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DOI：
10.1038/onc.2009.378
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发表时间：
2010-02-11
期刊：
影响因子：
8
通讯作者：
Cazaux, C.
中科院分区：
文献类型：
--
作者：
Pillaire, M-J;Selves, J.;Cazaux, C.
结直肠癌是世界上最常见的癌症之一。作为肿瘤淋巴结转移（TNM）分期分类，在许多情况下，阳离子不允许预测患者的生存，需要额外的预后因素来更好地预测其结果。参与DNA复制的基因可能代表了这种预后标记物的一个未充分探索的来源。事实上，DNA复制过程中的意外事件会引发“复制压力”，这是癌症早期阶段的主要特征之一。在这项研究中，我们评估了来自74名患者的同质系列的原发性肿瘤和邻近正常组织中47个“DNA复制”基因的表达。我们发现，编码跨病变（TLS）DNA聚合酶，DNA复制的起始，S期信号和复制叉的保护基因在肿瘤中显着失调。我们还观察到，MCM 7解旋酶或TLS DNA聚合酶POLQ的过表达（如果也与伴随的环基因）与患者生存率差显著相关。我们的数据表明，存在一个“DNA复制签名”，可能代表一个新的预后标志物的来源。这样的特征可以帮助理解结直肠癌患者肿瘤进展的分子机制。Oncogene（2010）29，876-887; doi：10.1038/onc.2009.378; 2009年11月9日在线发表
Colorectal cancer is one of the most frequent cancers worldwide. As the tumor-node-metastasis (TNM) staging classi. cation does not allow to predict the survival of patients in many cases, additional prognostic factors are needed to better forecast their outcome. Genes involved in DNA replication may represent an underexplored source of such prognostic markers. Indeed, accidents during DNA replication can trigger 'replicative stress', one of the main features of cancer from earlier stages onward. In this study, we assessed the expression of 47 'DNA replication' genes in primary tumors and adjacent normal tissues from a homogeneous series of 74 patients. We found that genes coding for translesional (TLS) DNA polymerases, initiation of DNA replication, S-phase signaling and protection of replication forks were significantly deregulated in tumors. We also observed that the overexpression of either the MCM7 helicase or the TLS DNA polymerase POLQ (if also associated with a concomitant overexpression of. ring genes) was significantly related to poor patient survival. Our data suggest the existence of a 'DNA replication signature' that might represent a source of new prognostic markers. Such a signature could help in understanding the molecular mechanisms underlying tumor progression in colorectal cancer patients. Oncogene (2010) 29, 876-887; doi:10.1038/onc.2009.378; published online 9 November 2009