摘要
目的探讨细胞周期蛋白依赖性激酶抑制剂3(CDKN3)在人乳头瘤病毒16(HPV16)阳性宫颈癌中的表达及意义。方法检索并下载基因表达谱交互式分析(GEPIA)平台CDKN3在泛癌中的表达情况,并比较正常宫颈组织(13份)和宫颈癌组织(306份)CDKN3表达水平;再访问并下载基因表达综合(GEO)数据库中HPV16阳性宫颈癌GSE39001数据集,比较HPV16阳性宫颈癌组织(43份)与正常宫颈组织(12份)CDKN3 mRNA表达水平;通过免疫组织化学法检测贵州医科大学附属医院12例HPV16阳性宫颈癌、12例HPV16阳性宫颈癌前病变、10例HPV16阳性慢性宫颈炎患者及7例HPV阴性正常宫颈者组织CDKN3表达情况;选取宫颈癌SiHa(HPV16阳性)、HeLa(HPV18阳性)、HCC94(HPV阴性)细胞株,使用Western blot检测其CDKN3表达差异。结果GEPIA平台分析结果显示,CDKN3在泛癌中高表达,且宫颈癌组织CDKN3表达水平明显高于正常宫颈组织(P<0.05);GEO数据集分析结果发现,HPV16阳性宫颈癌组织CDKN3 mRNA相对表达水平明显高于正常宫颈组织(P<0.001);免疫组织化学验证发现,HPV16阳性宫颈癌、HPV16阳性宫颈癌前病变、HPV16阳性慢性宫颈炎及HPV阴性正常宫颈组织CDKN3阳性表达率分别为91.7%、58.3%、0、0;宫颈癌细胞Western blot检测结果显示,宫颈癌SiHa(HPV16阳性)细胞CDKN3表达水平明显高于HeLa(HPV18阳性)和HCC94(HPV阴性)细胞(P<0.05)。结论CDKN3可能是HPV16阳性宫颈癌中一种潜在的致癌基因,可作为一种宫颈癌前病变及宫颈癌筛选标志物,并为后续的机制研究及靶向治疗提供理论基础。
Objective To investigate the expression and significance of cyclin dependent kinase inhibitor 3(CDKN3)in human papillomavirus type 16(HPV16)-positive cervical cancer.Methods CDKN3 expression in pan-cancer was retrieved and downloaded from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,and the expression levels of CDKN3 between normal cervical tissues(13 samples)and cervical cancer tissues(306 samples)were compared.Subsequently,GSE39001 data of HPV16-positive cervical cancer was sourced and downloaded from the Gene Expression Omnibus(GEO)database,and the expression levels of CDKN3 mRNA in HPV16-positive cervical cancer tissues(43 samples)and normal cervical tissues(12 samples)were compared.Immunohistochemical method was used to detect the expression of CDKN3 in 12 cases of HPV16-positive cervical cancer,12 cases of HPV16-positive cervical precancerous lesions,10 cases of HPV16-positive chronic cervicitis and 7 cases of HPV-negative normal cervical samples collected from the Affiliated Hospital of Guizhou Medical University.SiHa(HPV16-positive),HeLa(HPV18-positive)and HCC94(HPV-negative)cervical cancer cell lines were selected,and their CDKN3 expression were detected by Western blot.Results The GEPIA platform analysis showed that CDKN3 was highly expressed in pan-cancer,and the expression level of CDKN3 in cervical cancer tissue was significantly higher than that in normal cervical tissue(P<0.05).The GEO dataset reflected a significantly increased CDKN3 mRNA expression level in HPV16-positive cervical cancer compared to normal cervical tissue(P<0.001).Immunohistochemical verification showed that the positive expression rates of CDKN3 in HPV16-positive cervical cancer,HPV16-positive cervical precancerous lesion,HPV16-positive chronic cervicitis and HPV-negative normal cervical tissues were 91.7%,58.3%,0 and 0,respectively.Western blot analysis of cervical cancer cells showed that the expression level of CDKN3 in SiHa(HPV16-positive)cells was significantly higher than that in HeLa(HPV18-positive)and HCC94(HPV-negative)cells(P<0.05).Conclusion CDKN3 is a new oncogene of HPV16-positive cervical cancer,which may be used as a marker of cervical precancerous lesions and cervical cancer screening,and may provide a theoretical basis for subsequent mechanism research and targeted therapy.
作者
谯坤
徐殿琴
朱小雨
周鑫竹
张瑜
谭玉洁
QIAO Kun;XU Dianqin;ZHU Xiaoyu;ZHOU Xinzhu;ZHANG Yu;TAN Yujie(School of Clinical Laboratory Science,Guizhou Medical University,Guiyang,Guizhou 550004,China;Department of Hypertension,the Affiliated Hospital of Guizhou Medical University,Guiyang,Guizhou 550004,China;Clinical Laboratory Center,the Affiliated Hospital of Guizhou Medical University,Guiyang,Guizhou 550004,China)
出处
《重庆医学》
CAS
2024年第5期651-656,共6页
Chongqing medicine
基金
国家自然科学基金地区项目(81960473)。
