CD47的表达与宫颈病变程度的相关性分析

Correlation analysis between the expression of CD47 and the degree of cervical lesions

目的探讨CD47的表达与宫颈病变的相关性。方法基于TCGA,TCGA Target GTEx数据库中宫颈组织mRNA序列分析CD47在宫颈癌组织及正常宫颈组织的表达,绘制预后生存曲线。GEO数据库宫颈组织mRNA序列分析比较无HPV感染与HPV 16/18感染宫颈组织中CD47表达,进一步比较HPV 16/18感染后不同病变程度宫颈组织中CD47表达。收集320例宫颈癌筛查(HPV分型检测、E6/E7 mRNA检测)患者的阴道镜宫颈活检组织病理切片,免疫组化SP检测CD47的表达水平,分析HPV 16/18、病理等级与CD47的相关性。结果生物信息分析及免疫组化提示与正常宫颈组织相比,CD47在HSIL及宫颈癌组织呈高表达,高表达的CD47与宫颈癌的预后相关。HPV 16/18感染后CD47的表达水平升高(t=2.494,P<0.05),且随着宫颈病变程度增高,CD47的表达水平随之增高(F=4.351,P<0.05;r_(s)=0.278,P<0.001)。HPV 16/18感染后E6/E7 mRNA(+)组CD47的表达水平高于E6/E7 mRNA(-)组(t=5.710,P<0.0001),其拷贝量与宫颈病变程度及CD47的表达水平呈正相关(F=15.557,P<0.0001;r_(s)=0.649,P<0.0001)(r_(s)=0.73,P<0.0001)。结论CD47在HPV 16/18感染后HSIL和宫颈癌呈高表达,其表达水平随宫颈病变程度而增高,且表达水平与E6/E7 mRNA相关。CD47是宫颈病变进展及治疗的潜在靶点。

Objective To investigate the correlation between CD47 and cervical lesions.Methods The expression and overall survival of CD47 in cervical cancer was analyzed using TCGA and TCGA Target GTEx databases.Based on GEO databases,the expression of CD47 was analyzed between cervical sample infected by HPV 16/18 and non-HPV.The differences of CD47 expression in the degrees of cervical lesions infected by HPV 16/18 were compared.The patholgical sections of colposcopy biopsy came from 320 patients who were admitted cervical cancer screening,including HPV typing and E6/E7 mRNA detection.Immunohistochemistry were used to determine CD47 expression,and histochemistry score(H-score)was used to quantify the levels of CD47.The correlation among HPV 16/18,pathological grades and CD47 was analyzed.Results Bioinformatics tool analysis and immunohistochemistry showed that CD47 was up-regulated in HSIL and CC,associated with the prognosis of CC.The expression levels of CD47 in cervical tissues increased significantly after HPV 16/18 infection(t=2.494,P<0.05),and in HPV 16/18 infected tissues,with the increase of pathological grades.The expression levels of CD47 significantly increased(F=4.351,P<0.05;r_(s)=0.278,P<0.001).The expression of CD47 in the E6/E7 mRNA(+)was higher than that in the E6/E7 mRNA(-)(t=5.710,P<0.0001),and the copies of E6/E7 were related to the degree of cervical lesions,and were positively correlated with the expression level of CD47(F=15.557,P<0.0001;r_(s)=0.649,P<0.0001)(r_(s)=0.73,P<0.0001).Conclusion CD47 is overexpressed in HSIL and CC after HPV 16/18 infection.The expression levels of CD47 increases with the degree of cervical lesions,and is correlated with E6/E7 mRNA.CD47 may be a potential target for cervical disease progression and therapy.