Identification of prognostic biomarkers for response to radiotherapy by DNA microarray in nasopharyngeal carcinoma patients
Identification of prognostic biomarkers for response to radiotherapy by DNA microarray in nasopharyngeal carcinoma patients
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DNA 微阵列鉴定鼻咽癌患者放疗反应的预后生物标志物
DOI：
10.3892/ijo.2012.1341
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发表时间：
2012-05-01
影响因子：
5.2
通讯作者：
Li, Yao
中科院分区：
文献类型：
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作者：
Yang, Shu;Chen, Jiaxin;Li, Yao
鼻咽癌（Nasopharyngealcarcinoma，NPC）是一种恶性肿瘤，其发病率在世界范围内有着不寻常的变化.放射治疗是鼻咽癌的主要治疗方式，但在许多情况下，放射抵抗仍然是成功治疗的严重障碍。为了确定参与这种抵抗的基因，并找到预测鼻咽癌放疗反应的分子标记物，我们使用DNA微阵列比较了12例放射抵抗患者活检标本和8例放射敏感患者活检标本的表达谱，其中包含14112个人类unigenes。共检测到111个异常表达基因，其中ZNF608和CSFIR基因在放射抵抗型鼻咽癌中的表达高于放射敏感型鼻咽癌。通过生物统计学和生物信息学分析，发现26条（9大类）可能与鼻咽癌辐射抗性相关的途径，包括细胞离子稳态、细胞增殖、受体蛋白信号转导、膜系统、体液免疫应答、细胞因子和炎症反应等。提示鼻咽癌抗辐射能力的产生主要是由于放疗后细胞内钙稳态的改变，促进抗凋亡、DNA修复和挽救肿瘤细胞。由细胞外和细胞内因子诱导的细胞增殖促进可能在放疗下维持肿瘤大小，导致治疗后复发。我们的研究表明，至少有两个异位表达的基因在鼻咽癌放疗的预后中起重要作用，并可能成为未来新的放射治疗策略的潜在靶点。
Nasopharyngeal carcinoma (NPC) is a malignancy with an unusually variable incidence rate across the world. Radiotherapy is the primary treatment modality for NPC, but radiation resistance remains a serious obstacle to successful treatment in many cases. To identify the genes involved in this resistance and to find molecular markers for predicting NPC response to radiotherapy, we compare the expression profiles of 12 radiation-resistant patient biopsy specimens and 8 radiation-sensitive patient biopsy specimens using DNA microarray, containing 14112 human unigenes. A total of 111 aberrantly expressed genes were identified, of which ZNF608 and CSFIR were up-regulated in the radiation-resistant NPC compared with radiation-sensitive NPC, and the results were confirmed by real-time RT-PCR in 17 independent NPC patient specimens. Biostatistics and bioinformatics analyses were performed to detect the potential pathway underling this resistance, 26 pathways (9 categories) were found probably associated with radiation-resistant NPC, such as cell ion homeostasis, cell proliferation, receptor protein signalling, membrane system, humoral immune response, as well as cytokines and inflammation. We suggest the radiation-resistant capacity of NPC was mostly due to the change of cell Ca2+ homeostasis promoting anti-apoptosis, DNA repair and rescuing tumour cells under radiation therapy. Cell proliferation promotion induced by extracellular and intracellular factors may maintain tumour size under radiotherapy leading to recurrence after treatment. Our study reveals that at least 2 ectopically expressed genes play important roles in prognosis of NPC radiotherapy and may serve as potential targets for novel radiation therapeutic strategies in the future.