【摘要】 目的利用基因芯片技术筛选出与预测子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)发展成子宫颈癌危险性相关的差异表达基因。方法收集3例病理诊断为子宫颈癌的新鲜标本,分为正常组、CIN1、CIN2/3及子宫颈癌4组(共12个样本),利用Illumina Bead Chip平台对其进行全基因组表达谱分析。结果与正常组相比,CIN1组中有41个上调基因,105个下调基因;CIN2/3组中有57个上调基因,16个下调基因;子宫颈癌组中有1 137个上调基因,513个下调基因。在CIN1和CIN2/3中有13个基因(ANKRD20A1、OLFM4、SNORD46、LOC642333、C13orf30、ASB5、C6、CABP4、POU5F1P1、DNHD2、LR-RC50、C1orf87和CCDC17)共同上调,4个基因(DEFB103B、IL6、CDC45L和E2F2)共同下调。而ANKRD20A1、DEFB103B和IL6在CIN1、CIN2/3和子宫颈癌各组中均共同上调或下调。结论在子宫颈癌发生的早期阶段,ANKRD20A1、OLFM4、SN-ORD46、LOC642333、C13orf30、ASB5、C6、CABP4、POU5F1P1、DNHD2、LRRC50、C1orf87及CCDC17等基因的上调具有重要作用。对上述差异基因的检测可能对评估CIN病变尤其是CIN1发展为子宫颈癌的危险性具有帮助,从而减少由于子宫颈病变的异质性和子宫颈活检技术的局限性所导致的CIN2/3漏诊,同时指导临床医师对CIN1进行更合理的管理和治疗。更多还原

【Abstract】 Purpose The aim of this study was to identify new genomic biomarkers by gene microarray technique for predicting the risk of cervical intraepithelial neoplasia(CIN) developing into cervical cancer.Methods 12 fresh specimens were collected from 3 cervical carcinoma patients.According to the diagnosis of frozen section,four specimens from the same patient were divided into four groups of normal,CIN1,CIN2/3 and cervical cancer.Illumina’s gene expression Bead Chip was used for whole-genome expression analysis.Results Compared to the normal group,we have detected 41 genes up-regulated and 105 genes down-regulated in CIN1 tissues,57 genes up-regulated and 16 genes down-regulated in CIN2/3 tissues,1 137 genes up-regulated and 513 genes down-regulated in cervical cancer tissues.Among these differentially expressed genes,13 genes(ANKRD20A1,OLFM4,SNORD46,LOC642333,C13orf30,ASB5,C6,CABP4,POU5F1P1,DNHD2,LRRC50,C1orf87,and CCDC17) were found up-regulated and 4(DEFB103B,IL6,CDC45L and E2F2) down-regulated in both CIN1 and CIN2/3 tissues.Furthermore,we characterized an up-regulated gene(ANKRD20A1) and 2 down-regulated genes(DEFB103B and IL6) through the development of CIN1,CIN2/3 and cervical cancer.Conclusions Our study suggested that the over-expression of ANKRD20A1,OLFM4,SNORD46,LOC642333,C13orf30,ASB5,C6,CABP4,POU5F1P1,DNHD2,LRRC50,C1orf87,and CCDC17 genes were involved in the progression of CIN lesions.This result indicated that the risk of CIN developing into cervical cancer could be prognosed by testing these molecular makers and minimize the missed diagnosis of CIN2/3 due to the heterogeneity of CIN lesions and the limitations of cervical biopsy.更多还原