糖链结构在呼吸道乳头状瘤病发病中作用机制的初步研究

目的 比较复发性呼吸道乳头状瘤病(recurrent respiratory papillomatosis,RRP)与声带息肉糖链结构相关基因表达的差异,研究人乳头状瘤病毒(human papillomavims,HPV)致呼吸道乳头状瘤病的分子机制.方法 利用mRNA平行扩增和人全基因组芯片分析比较3组(6例样本)成人声带息肉与喉乳头状瘤病组织基因表达谱的差异,水平聚类分析、国际基因数据库功能基因注释及path way分析,获得与HPV感染致RRP的相关基因.结果 水平聚类3组表达谱芯片数据获得567个HPV致RRP发病相关基因.一系列糖复合物的糖链结构相关基因发生变化:N-连接糖链核心结构生成催化酶长萜基磷酸-甘露糖转移酶多肽1(doliehyl-phosphate mannosyltransferase polypeptide 1,DPM1)、天冬酰胺连接糖基化1同源物(asparagine-linked glycosylation 1 homolog,ALG1)、岩藻糖基转移酶(fucosyltransferase 8,FUT8)和α甘露糖苷酶(α-mannosidase 1A,MAN1A)基因表达受调控;N-糖苷键寡聚糖链降解水解酶β氨基己糖苷酶(β-hexosaminidase,HEXB)和半乳糖苷酶1(β1-galactosidase,GLB1)基因表达显著下调;抗凝型硫酸肝素的合成限速酶3-O-磺基转移酶(heparan sulfate 3-O-sulfotransferase 1,HS3ST3A1)显著上调,硫酸肝素链延伸的关键酶之一糖基转移酶软骨瘤1(exostoses 1,EXT1)基因显著下调;影响Ⅰ型硫酸角质素合成的岩藻糖基转移酶(fucosyltransferase,FUT)基因表达显著下调;细胞膜重要组成的糖鞘脂类相关酶β3-N乙酰葡糖氨基转移酶4(β-3-3-N-acetylglucosaminyhransferase 4,B3GNT4)及尿苷二磷酸-神经酰胺葡糖基转移酶(UDP-glucose ceramide glucosyltransferase,UGCG)编码基因显著上调.结论 与声带息肉比较,乳头状瘤细胞中合成和降解相关糖链分子结构单位的酶编码基因发生改变,这可能是HPV感染致瘤形成的始动环节.

Primary study on glycan structure in pathopoiesis mechanism of recurrent respiratory papillomatosis

OBJECTIVE: To compare the molecular basis difference between recurrent respiratory papillomatosis (RRP) and vocal cord polyp, to analyze the expression of glycan structural genes, and to discuss the pathopoiesis mechanism of RRP. METHODS: The gene expressing profile between the 3 groups papilloma and the vocal cord polyp regarded as normal larynx epithelium were compared using mRNA parallel amplify and the human genome gene expressing microarray. Through cluster analysis, Gene Ontology function gene annotation and path way analysis, the relative gene of RRP and HPV infection were acquired. RESULTS: According to three microarrays results, total 567 expression changed genes related to HPV induce RRP were acquired. A serial change of glycan structure biosynthesis and degradation pathways was significant. The expression of dolichyl-phosphate mannosyltransferase polypeptide 1 (DPM1), asparagine-linked glycosylation 1 homolog (ALG1), fucosyltransferase 8 (FUT8) and alpha-mannosidase 1A (MAN1A) were regulated and beta-hexosaminidase (HEXB), beta1-galactosidase (GLB1), exostoses 1 (EXT1), fucosyltransferase (FUT) reduced expression and heparan sulfate 3-O-sulfotransferase 1 (HS3ST3A1) increased expression. The two related enzymes of the glycosphingolipids which is the main composed of the cell membrane, beta-3-N-acetylglucosaminyltransferase 4 (B3GNT4) and UDP-glucose ceramide glucosyltransferase (UGCG) increase expression, HEXB and GLB1 reduced expression. CONCLUSIONS: The alteration of the coding genes of glycan structure biosynthesis and degradation pathways were significantly and characteristically in pathopoiesis mechanism of RRP. This abnormality may be the beginning of tumor form HPV infection.