摘要
目的 探讨红细胞叶酸和p16基因表达与子宫颈癌发生发展的关系以及二者的交互效应.方法 选择经病理学确诊的子宫颈炎(CI)患者58例、低度子宫颈上皮内瘤变(CIN Ⅰ)患者52例、高度子宫颈上皮内瘤变(CINⅡ~Ⅲ)患者60例和子宫颈鳞状细胞癌(SCC)患者76例作为研究对象.在收集人口学特征和子宫颈病变相关因素的基础上,检测红细胞叶酸水平(微生物法)、人乳头状瘤病毒16(HPV16)的感染状况(PCR法)、子宫颈组织中p16基因mRNA(实时定量PCR法)和蛋白表达水平(Western blot法).结果 红细胞叶酸水平在CI组为(285.66±48.08) ng/ml,CIN Ⅰ组为(268.70±46.01) ng/ml,CINⅡ~Ⅲ组为(251.22±32.20)ng/ml,SCC组为(226.21±44.79)ng/ml,随着子宫颈病变程度的加重,红细胞叶酸水平呈下降趋势(x 2趋势=32.39,P< 0.001);p16 mRNA及蛋白表达水平逐渐升高(x 2趋势=24.68,P< 0.001;x2趋势=45.84,P<0.001);红细胞叶酸与p16mRNA及蛋白表达均呈负相关关系(r=-0.114,P< 0.001;r=-0.192,P< 0.001).交互作用分析显示,红细胞叶酸缺乏与p16 mRNA及蛋白高表达在CIN Ⅰ组、CINⅡ~Ⅲ组及SCC组均显示正相加交互作用.结论 红细胞叶酸缺乏和p16 mRNA及蛋白高表达均可增加子宫颈癌变发生的风险,两者在子宫颈癌及其癌前病变中可能存在正相加交互作用.
Objective To explore the interaction effects between blood folate and p16 gene expression in the progression of cervical cancerization.Methods The study participants included 58 patients with cervical inflammation (CI),52 patients with cervical intraepithelial neoplasm Ⅰ (CIN Ⅰ),60 patients with cervical intraepithelial neoplasm Ⅱ-Ⅲ (CIN Ⅱ-Ⅲ) and 76 patients with cervical squamous cell carcinoma (SCC),who were diagnosed by pathology.On the basis of collecting the demography information and cervical cancerization factors by structured questionnaire,blood folate levels were detected by microbiological assay,HPV16 infection status was determined by PCR,the expressions of p16 mRNA and protein were detected by real-time PCR and Western blot,respectively.Results The level of blood folate was (285.66±48.08) ng/ml in CI group,(268.70±46.01) ng/ml in CIN Ⅰ group,(251.22±32.20) ng/ml in CINⅡ-Ⅲ group,(226.21±44.79) ng/ml in SCC group.Blood folate levels were decreased gradually with the deterioration of the cervical lesion (x2trend =32.39,P 〈 0.001),whereas levels of p16 mRNA expression (x2trend =24.68,P 〈 0.001) and protein expression (x2trend =45.84,P 〈 0.001) were increased.The levels of blood folate were negatively correlated with p16 mRNA expression (r =-0.114,P 〈 0.001) or protein expression (r =-0.192,P 〈 0.001),and there was an additive interaction between blood folate deficiency and p16 mRNA or protein expression in CIN and SCC as well.Conclusions Both blood folate deficiency and high expression of p16 mRNA or protein could increase the risk of cervical cancerization,there may be a synergistic action between blood folate and p16 in the progression of cervical cancerization.
出处
《肿瘤研究与临床》
CAS
2015年第4期228-233,242,共7页
Cancer Research and Clinic
基金
国家自然科学基金(30872166、81273157)
山西省自然科学基金(2008011075-1)