宫颈癌组织IEX-1表达及其与HPV感染相关性研究  

Expression of IEX-1 in cervical cancer and the relationship with HPV infection

作　　者：张庆庆[1] 韩丽萍[1] 余海洋[1] 刘丽雅[1] 李元[1] 

机构地区：[1]郑州大学第一附属医院妇科.河南省高等学校临床医学重点学科开放实验室,河南郑州450052

出　　处：《中华肿瘤防治杂志》2017年第2期93-97,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：河南省科技厅重点攻关项目(122102310631)

摘　　要：目的即刻早期反应基因(immediate early response gene X-1,IEX-1)是一种凋亡易感基因,在多种人类恶性肿瘤中表达失调,但在宫颈癌组织中的表达相关研究较少,检测宫颈癌组织IEX-1的表达,了解其在宫颈癌发生发展中的作用,分析其与人乳头瘤病毒(human papillomavirus,HPV)感染的关系。方法收集2011-01-01-2015-10-31郑州大学第一附属医院病理科存档蜡块标本132份,采用免疫组化法检测IEX-1在宫颈癌、宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及良性宫颈病变组织中的表达情况,分析IEX-1的表达与宫颈癌临床病理关系。采用RT-qPCR法及蛋白质印迹法检测Siha(HPV16+)、HeLa(HPV18+)和C-33a(HPV-)3种宫颈癌细胞株中IEX-1mRNA及蛋白的表达,siRNA法靶向沉默E6后Siha细胞E6、IEX-1的mRNA及蛋白表达,分析与HPV感染的关系。结果 IEX-1在宫颈良性病变、CIN组织和宫颈癌组织中的表达分别为72.4%、58.7%和21.1%,差异有统计学意义,χ~2=21.345,P=0.001。宫颈癌组织IEX-1的表达与患者年龄、病理类型、HPV感染型别及FIGO分期无关,均P>0.05。IEX-1的表达与宫颈癌分化程度、淋巴结转移情况及宫旁浸润密切相关,均P<0.05。C-33a细胞中IEX-1mRNA表达量为21.652±9.020,明显高于Siha细胞的1(t=7.34,P<0.001)和HeLa细胞的1.742±0.854(t=6.21,P<0.001);IEX-1蛋白表达量为18.017±1.351,明显高于Siha细胞的1.519±0.391(t=8.16,P<0.001)和HeLa细胞的1.957±0.363(t=7.19,P<0.001)。干扰组E6mRNA水平为0.218±0.106,低于阴性对照组的1.031±0.072(t=9.21,P<0.001)和空白对照组(t=8.46,P<0.001);干扰组E6蛋白表达量为0.184±0.274,低于阴性对照组的0.692±0.133(t=8.71,P<0.001)和空白对照组的0.783±0.097(t=8.06,P<0.001)。干扰组IEX-1mRNA水平为20.083±0.672,低于阴性对照组的1.193±0.408(t=9.04,P<0.001)和空白对照组,t=7.56,P<0.001;干扰组IEX-1蛋白表达量为0.672±0.135,低于阴性对照组的0.137±0.071(t=7.92,P<0.001)和空白对照组的0.081±OBJECTIVE Immediate early response gene （immediate early response gene X-1, IEX-1） is sensitive to apoptosis gene and disorders in a variety of human malignant tumors, but the related researches in cervical cancer is rare. This study aimed to investigate the expression IEX-1 and the relationship with genesis and development of cervical cancer, and explore the correlation between expression of IEX-1 and HPV infection. METHODS Totally 132 Paraffin block spec- imens were collected from January 2011 to October 2015 in the First Affiliated Hospital of Zhengzhou University. The ex- pressions of IEX-1 in cervical cancer, cervical intraepithelial neoplasia（CIN）and benign lesion cervical tissue were meas- ured by immunohistochemistry. The clinical significance of IEX-1 expression was analyzed with clinical pathological fea- tures of cervical cancer. The expressions of IEX-1, IEX-1 protein in Siha （I-IPV16 ＋ ）, HeLa （HPV18 ＋ ） and C-33a （HPV--）were detected by the RT-qPCR and the Western Blot. RESULTS The expressions of IEX-1 in cervical benign lesion, precancerous lesions and cervical carcinoma were 72. 4%, 58. 7% and 21. 1%. The difference was statisticallysignificant （x2 =21. 345 ,P〈0. 017）. The expression of IEX-1 in cervical cancer was independent of the age, pathological type, HPV subtype and FIGO stage （P〉0.05）. The expression of IEX-1 was closely correlated with cell differentiation, lymph node metastasis and parametrial invasion. IEX-lmRNA and IEX-1 protein expression in C-33a cells （21. 652 ± 9. 020） was higher than that inSiha （t=7.34,P〈0. 001） and HeLa cells（1.742±0.854, t=6.21,P〈0.001）. The ex- pression of IEX 1 protein （18. 017±1. 351） was significantly higher than that in Siha cells （1. 519±0. 391.4, t 8.16, P〈0.001） and HeLa ceils （1. 957±0. 363, t=7. 19, P〈0. 001）. The level of E6 mRNA in the interfering group （0. 218±0. 106） was lower than that in the negative control group （1. 031±0. 072, t=9.21, P〈0. 001） and the blank

关 键 词：宫颈癌 即刻早期反应基因-1 人乳头瘤病毒 宫颈上皮内瘤变 

分 类 号：R737.33[医药卫生—肿瘤]