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目的筛查声门上喉癌发生、发展及转移相关的异常染色体和重要基因。方法应用比较基因组杂交(comparative ge-nomic hybridization,CGH)分析喉声门上鳞状细胞癌(laryngeal squamous cell cancer,LSCC)癌组织和癌旁组织DNA拷贝数的差异。应用cDNA芯片结合聚类分析研究喉声门上癌癌旁组织、癌组织和转移淋巴组织中差异表达的基因。结果CGH结果表明每例喉癌平均涉及12.9个染色体的异常,其中出现高频率扩增的染色体区集中在3q15-21(14/18)、5p12-13(11/18)、8q22-24(6/18)、11q12-13(8/18)、15q21-23(7/18)and18p11(8/18),而高频率缺失的染色体区集中在1p13-21(8/18)、3p21-23(14/18)、5q21-22(14/18)、9p12-pter(11/18)and13q21-31(8/18)。聚类分析将表达差异的基因分为3组。表达差异在5倍以上的基因12个,在由癌旁至癌阶段、癌至转移阶段均存在表达异常的基因3个。这15个重要基因是喉癌新的相关基因,其中4个基因cytochrome C oxidaseⅤa,PPBP,EPHX2and PON1与喉癌相关性的研究未见报道,而且,SH3GL2位于高频率缺失的染色体区9p12-pter。结论我们发现的特异染色体区和重要基因将为喉癌发生、发展和转移的研究提供重要线索。
Objective To screen abnormal chromosomes and important genes related to the occurrence, development and metastasis of supraglottic laryngeal cancer. Methods The comparative genomic DNA hybridization (CGH) was used to analyze the difference of DNA copy number between laryngeal squamous cell carcinoma (LSCC) and adjacent non-cancerous tissues. CDNA microarray combined with cluster analysis was used to study differentially expressed genes in the supratentorial cancer tissues, cancer tissues and metastatic lymphoid tissues. Results CGH results showed that each laryngeal cancer involved an average of 12.9 chromosome abnormalities. Among them, chromosome regions with high frequency amplification were found in 3q15-21 (14/18), 5p12-13 (11/18), 8q22-24 / 18), 11q12-13 (8/18), 15q21-23 (7/18) and18p11 (8/18), whereas the high frequency deletion of the chromosomal region was concentrated at 1p13-21 (8/18), 3p21-23 14/18), 5q21-22 (14/18), 9p12-pter (11/18) and 13q21-31 (8/18). Cluster analysis divided the genes that expressed the differences into three groups. There were 12 genes with more than 5-fold difference in expression, and 3 genes were abnormal in both cancer-to-cancer and cancer-to-metastasis stages. These fifteen important genes are new related genes of laryngeal cancer, of which four genes related to cytochrome C oxidase Va, PPBP, EPHX2 and PON1 have not been reported, and SH3GL2 is located in 9p12-pter with high frequency deletion. Conclusion The specific chromosomal regions and important genes that we found will provide important clues for the study on the occurrence, development and metastasis of laryngeal cancer.