Genetic Instability and Cancer Group, Department Biology of Cancer, Institute of Pharmacology and Structural Biology, UMR5089 CNRS, University of Toulouse, University Paul Sabatier, Toulouse, France.
Oncogene. 2010 Feb 11;29(6):876-87. doi: 10.1038/onc.2009.378. Epub 2009 Nov 9.
Colorectal cancer is one of the most frequent cancers worldwide. As the tumor-node-metastasis (TNM) staging classification 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 firing 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.
结直肠癌是全球最常见的癌症之一。由于肿瘤-淋巴结-转移（TNM）分期分类在许多情况下无法预测患者的生存情况，因此需要额外的预后因素来更好地预测他们的结局。参与 DNA 复制的基因可能代表了这种预后标志物尚未被充分探索的来源。事实上，DNA 复制过程中的事故可能会引发“复制应激”，这是癌症从早期阶段开始的主要特征之一。在这项研究中，我们评估了 74 名患者的同源系列原发性肿瘤和相邻正常组织中 47 个“DNA 复制”基因的表达情况。我们发现，跨损伤（TLS）DNA 聚合酶、DNA 复制起始、S 期信号和复制叉保护的基因编码均在肿瘤中显著失调。我们还观察到，MCM7 解旋酶或 TLS DNA 聚合酶 POLQ 的过表达（如果与起始基因的同时过表达相关）与患者的不良生存显著相关。我们的数据表明存在一种“DNA 复制特征”，它可能是新的预后标志物的来源。这种特征可以帮助我们理解结直肠癌患者肿瘤进展的分子机制。
