Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China
Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China
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中国南方鼻咽癌的转录模式、生物标志物和通路特征
DOI：
10.1186/1479-5876-6-32
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发表时间：
2008-06-20
影响因子：
7.4
通讯作者：
Yao, Kaitai
中科院分区：
文献类型：
--
作者：
Fang, Weiyi;Li, Xin;Yao, Kaitai
背景资料：鼻咽癌的发病是一个涉及遗传易感性、EB病毒感染和基因改变的复杂过程。虽然一些癌基因和肿瘤抑制基因已被报道在鼻咽癌，一个完整的理解的发病机制，鼻咽癌的背景下，全球基因表达，转录途径和生物标志物的评估仍有待阐明。将32例经病理证实的低分化鼻咽癌患者的总RNA分为4个连续样本池，每个样本池将来自24例正常非癌鼻咽组织（NP）的混合RNA与人8 KcDNA阵列平台共杂交。通过半定量RT-PCR和免疫组化方法验证微阵列数据的可靠性。结果：严格的统计过滤参数确定了435个基因在NPC中表达上调，257个基因表达下调。基于先前在各种癌症和不包括NPC或NP的正常组织之间的广泛比较，先前已经提出了包括CYCI、MIF、LAMB 3、TUBB 2、UBE 2C和TRAPI的七个上调基因作为候选的常见癌症生物标志物。此外，通过基于微阵列文献的注释搜索引擎MILANO，筛选出MIF、BIRC 5、PTTGI、ATM、FOXOIA、TGFBR 2、PRKARIA、KLF 5和PDCD 4等9个已知的癌基因和抑癌基因，提示这些基因可能特异性地参与鼻咽上皮恶性转化的促进。结果发现这些差异表达基因参与了细胞凋亡、MAPK、VEGF和B细胞受体信号通路等与细胞生长、信号转导和免疫系统激活相关的功能。结论：本研究筛选出了与鼻咽癌发生相关的几条通路的潜在候选生物标志物--癌基因/抑癌基因。这些信息有助于确定鼻咽癌的诊断和治疗靶点，并为鼻咽癌的分子发病机制提供见解。
Background: The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated.Methods: Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was cohybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry.Results: Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYCI, MIF, LAMB3, TUBB2, UBE2C and TRAPI had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTGI, ATM, FOXOIA, TGFBR2, PRKARIA, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation.Conclusion: This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC.