Gene expression changes in residual advanced cervical cancer after radiotherapy: indicators of poor prognosis and radioresistance?
Gene expression changes in residual advanced cervical cancer after radiotherapy: indicators of poor prognosis and radioresistance?
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DOI：
10.12659/msm.893689
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发表时间：
2015-05-05
期刊：
影响因子：
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通讯作者：
Cai JM
中科院分区：
文献类型：
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作者：
Fu ZC;Wang FM;Cai JM
中晚期宫颈癌对放疗的敏感性不同，在某些情况下会降低放疗的效果。我们试图找出差异表达的基因在宫颈癌放疗后残留，可能与不良预后和放射抵抗。应用寡核苷酸芯片技术检测宫颈癌组织在放疗前和50-戈伊剂量放疗后的基因表达差异。芯片结果通过实时荧光定量PCR进行验证。在放疗前石蜡包埋的宫颈癌组织中通过免疫组化验证CXCL 12。生存分析证实了该基因与预后的关系。分层聚类分析鉴定了238个表现出≥3.0倍变化且p<0.05的分化基因。与对照组相比，我们发现在50-戈伊剂量的辐射后，111个基因持续上调，127个基因持续下调。这些基因参与细胞生长和死亡、细胞凋亡、细胞周期调控、细胞信号传导、DNA合成和修复以及细胞粘附等过程。放射治疗前后CXCL 12、CD 74、FGF 7、COL 14 A1、PRC 1和RAD 54 L基因的高差异表达通过定量PCR验证。生存分析结果显示CXCL 12的高表达与预后不良密切相关。CXCL 12的高表达可能是接受根治性放射治疗的患者预后不良的信息。本研究所发现的差异表达基因可能为宫颈癌放射抵抗的诊断和治疗提供新的方法。
Different sensitivity of advanced cervical cancer to irradiation can decrease effectiveness of radiotherapy in some cases. We attempted to identify the differentially expressed genes in residual cervical cancer after radiotherapy that might be associated with poor prognosis and radioresistance. Differential genes expression was identified by an oligonucleotide microarray in cervical cancer tissues before radiation and after a 50-Gy dose of radiation. The microarray results were validated by quantitative real-time PCR. CXCL12 was validated by immunohistochemistry in paraffin-embedded cervical cancer tissues before radiotherapy. The relationship between the differentiated gene and prognosis was validated by survival analysis. Hierarchic cluster analysis identified 238 differentiated genes that exhibited ≥3.0-fold change and p<0.05. We found 111 genes that were in persistent up-regulation and 127 in persistent down-regulation after a 50-Gy dose of radiation when compared with the control group. These genes were involved in processes such as cell growth and death, cell-apoptosis, cell cycle regulation, cell signaling, DNA synthesis and repair, and cell adhesion. High differential expression of CXCL12, CD74, FGF7, COL14A1, PRC1, and RAD54L genes was validated by quantitative PCR before and after radiotherapy. Survival analysis results showed that the high expression of CXCL12 was closely related to poor prognosis. The higher expression of CXCL12 might be informative regarding poor prognosis in patients undergoing radical radiotherapy. The differentially expressed genes identified in our study might provide a new method for diagnosis and treatment of radioresistance in cervical cancer.