摘要
目的探讨维吾尔族妇女宫颈癌组织特异的下调表达基因谱,建立基于下调表达基因的宫颈癌早期诊断方法。方法收集维吾尔族妇女宫颈病变新鲜组织标本72例,其中宫颈鳞癌(cervical squamous cell carcino-ma,CSCC)25例,宫颈内上皮瘤变(cervical intraepithelial neoplasia,CIN)22例,正常宫颈组织(normal cervix,NC)25例。选择20例组织标本(CSCC 7例,CINⅢ6例,NC 7例),提取组织RNA,通过人类全基因组表达谱芯片及生物信息分析,筛选宫颈癌及癌前病变(CIN)特异性下调表达候选基因。通过对CSCC与正常对照(NC)组的基因差异表达谱进行比较分析,选取10种差异表达倍数较高的候选基因,利用72例宫颈病变组织RNA,对10种下调表达候选基因的表达水平进行半定量RT-PCR鉴定,确定宫颈癌及癌前病变与该基因表达水平变化的关系。结果以2倍及以上表达差异为量化标准,有下调表达候选基因112种。72例宫颈病变组织RNA的半定量RT-PCR筛查分析,发现在CSCC与正常对照组之间,FOSB、DNASE1L3、SCARA5、EGR1、ABI3BP、FOS、KLF4、RHOB、IER2和ID4等10种下调表达基因的差异均有统计学意义(P<0.05)。DNASE1L3、EGR1、FOS、KLF4和IER2等5种基因的表达水平差异在CIN与正常对照组之间有统计学意义(P<0.05),但是除了FOS基因外,其余4种基因表达在CSCC与CIN组之间无差异(P>0.05)。结论维吾尔族妇女宫颈癌发病进程可能与一系列基因的下调表达密切相关,而DNASE1L3、EGR1、FOS、KLF4和IER2等5种基因的表达水平变化可能成为宫颈癌早期预警指标。
Objective To study the gene expression profile downregulated in cervical cancer tissues of Uy-ghur women for the establishment of early diagnostic markers of cervical cancer based on downregulated genes. Methods Seventy two cases of fresh tissue specimens from Uyghur women with cervical lesions are selected, including twenty five cases of cervical squamous cell carcinoma （CSCC）, twenty two cases of cer-vical intraepithelial neoplasia （CIN） and twenty five cases of cervicitis or normal cervix （NC）. Twenty ca-ses of high quality tissue specimens （seven cases of CSCC, six cases of CIN HI and seven cases of NC） were selected for the screening of candidate downregulated genes specific to cervical carcinoma and its precursor lesions by extraction tissue of RNA and subsequent analysis with human genome-wide expression profile chip followed by bioinformatics investigation. Seventy two cases of tissue RNAs were subjected to the a- nalysis by semi-quantitative RT-PCR for the screening of ten candidate downregulated genes, to study the association of candidate gene expression with the development of cervical cancer and precursor lesions. Re-suits We identified 112 candidate genes downregulated in CSCC compared with control group （NC） by a-nalysis of the differentially expressed gene profile and setting up a difference of gene expression level of more than two times as standard. By bioinformatics analysis, literature review and other criteria, we se-lected 10 candidate genes downregulated in cervical cancer with relatively high difference including FOSB, DNASEIL3, SCARA5, EGR1, ABI3BP, FOS, KLF4, ID4, IER2 and RHOB and screened by analysis of 72 cases of tissue RNAs with semi-quantitative RT-PCR, and found that the expression of all genes above was downregualted with significant differences, when CSCC and NC were compared （P 〈0.05）, which confirmed that the data of gene expression profile analysis had a relatively high feasibility and accuracy. The transcription of genes DNASEIL3, EGR1, FOS, KLF4 and IER2 was significantly downregulated in CIN compared with NC （P〈0.05）, but no difference was found between CSCC and CIN except for FOS, which suggested that the detection of these genes may have an impact on the diagnosis of precancerous le-sions. Conclusion The development of cervical carcinoma of Uyghur women may be associated with a se- ries of downregulated genes. The changes in DNASEIL3, EGR1, FOS, KLF4 and IER2 expression may become markers for the early diagnosis of cervical carcinoma.
出处
《新疆医科大学学报》
CAS
2013年第7期912-917,共6页
Journal of Xinjiang Medical University
基金
国家自然科学基金(81060171)
关键词
宫颈鳞癌
维吾尔族妇女
下调表达基因
人类全基因组表达谱芯片
crvical squamous cell carcinoma
Uyghur women
downregulated genes
human genome-wideexpression profile chip
