Gene expression changes in cervical squamous cell carcinoma after initiation of chemoradiation and correlation with clinical outcome
Gene expression changes in cervical squamous cell carcinoma after initiation of chemoradiation and correlation with clinical outcome
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DOI：
10.1016/j.ijrobp.2007.10.068
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发表时间：
2008-05-01
影响因子：
7
通讯作者：
Buchholz, Thomas A.
中科院分区：
文献类型：
--
作者：
Klopp, Ann H.;Jhingran, Anuja;Buchholz, Thomas A.
目的：本研究旨在研究人实体瘤放化疗后早期基因表达的变化，以确定放化疗诱导的肿瘤基因表达变化以及肿瘤微环境。方法与材料：对2001年4月至2002年8月收治的12例宫颈鳞癌IB2~IIIB期患者放化疗前和放化疗后48h的基因表达谱进行基因芯片实验。结果：共鉴定出放化疗后显著变化的基因262个。与DNA修复相关的基因包括DDB2ERCC4、GADD45A和XPC。此外，显著调节的细胞间信号通路包括胰岛素样生长因子-1(IGF-1)、干扰素和血管内皮生长因子信号。中位随访时间为41个月，12名患者中有5名经历了局部或远处衰竭。监督聚类分析从治疗前样本中确定了58个基因集，这些基因在复发患者和无复发患者之间存在差异表达。在该基因集中发现了与整合素信号转导和细胞凋亡途径有关的基因。永生化上调蛋白(IMUP)、胰岛素样生长因子-2(IGF-2)和急性呼吸窘迫综合征(ARHD)在复发组和未复发组中的表达有显著差异。结论：基因图谱确定了化疗所调节的基因，包括DNA损伤和细胞间信号通路。确定了与复发相关的基因，需要在独立的患者数据集中进行验证，以确定与临床结果相关的58个基因集是否可以用作预后分析。(C)2008年爱思唯尔公司。
Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome.Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002.Results: A total of 262 genes were identified that were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence.Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay. (c) 2008 Elsevier Inc.