早期宫颈癌组织中ATG-12表达与HPV16-E6/E7-DNA病毒载量及预后的关系  

Relationship between ATG-12 and HPV16-E6/E7-DNA viral load and prognosis in early-stage cervical cancer

作　　者：吴霞[1] 桑学梅[1] 宋瑞[2] 胡怀远[2] 胡恒贵[2] 周芳芳[1] 马为为 姚小艳[1] WU Xia;SANG Xuemei;SONG Rui;HU Huaiyuan;HU Henggui;ZHOU Fangfang;MA Weiwei;YAO Xiaoyan(Department of Obstetrics and Gynecology,Anhui Wanbei Coal and Electricity Group General Hospital,the Third Affiliated Hospital of Bengbu Medical College,Suzhou 234000,China)

机构地区：[1]安徽皖北煤电集团总医院(蚌埠医学院第三附属医院)妇产科,安徽宿州234000 [2]安徽皖北煤电集团总医院(蚌埠医学院第三附属医院)病理科,234000

出　　处：《临床肿瘤学杂志》2020年第3期235-240,共6页Chinese Clinical Oncology

摘　　要：目的探讨早期宫颈癌组织中自噬相关蛋白-12(ATG-12)与人乳头瘤病毒(HPV)16-E6/E7-DNA病毒载量及预后的关系。方法选取2015年1月至2017年12月期间在安徽皖北煤电集团总医院保存的宫颈活检或手术切除宫颈组织203例,包括30例慢性宫颈炎、18例宫颈上皮内瘤变(CIN)Ⅰ、23例CINⅡ、26例CINⅢ和106例早期(ⅠA2~ⅡB期)宫颈鳞状上皮癌(CSCC)。采用巢式多重聚合酶链式反应(NM-PCR)和免疫组化染色SP法检测组织中HPV 16-E6/E7-DNA病毒载量和ATG-12蛋白表达。分析ATG-12蛋白表达与早期CSCC临床病理特征的关系。随访CSCC患者无瘤生存时间(DFS)。采用Cox风险比例回归模型分析影响CSCC预后的因素。结果CSCC组织ATG-12蛋白阳性表达率为26.42%(28/106),低于慢性宫颈炎和CIN组织(P<0.05)。ATG-12蛋白表达与HPV16-E6/E7-DNA病毒载量呈负相关(r=-0.306,P=0.001;r=-0.436,P=0.001)。ATG-12蛋白表达与FIGO分期、间质浸润、淋巴脉管间隙浸润、淋巴结转移有关(P<0.05)。随访11~64个月,ATG-12蛋白阳性表达患者5年无瘤生存率为78.57%(22/28),ATG-12蛋白表达阴性患者5年无瘤生存率为60.26%(47/78)。多因素Cox风险回归模型结果显示,HPV16-E6/E7-DNA病毒载量和ATG-12蛋白表达是影响患者DFS的独立预后因素(P<0.05)。结论早期宫颈鳞状上皮癌组织中ATG-12阳性表达率低,与HPV16-E6/E7-DNA病毒载量呈负相关,有望成为评估HPV阳性早期宫颈癌患者预后的重要指标。Objective To investigate the correlation between autophagy related protein-12(ATG-12)and HPV16-E6/E7-DNA viral load and prognosis in early cervical cancer.Methods From January 2015 to December 2017,203 cases of cervical biopsy or surgical removal were selected,including 30 cases of chronic cervicitis,18 cases of cervical intraepithelial neoplasia(CIN)I,23 cases of CIN II,26 cases of CIN III,106 cases of cervical squamous cell carcinoma(CSCC)in early stage(IA2-IIB),were selected.HPV16-E6/E7-DNA viral load and ATG-12 protein expression were detected by nested multiple polymerase chain reaction(NM-PCR)and SP immunohistochemical staining.The relationship between ATG-12 protein expression and the clinicopathological characteristics of early CSCC was analyzed.CSCC patients without tumor survival time(DFS)were followed-up.Cox regression model was used to analyze the prognostic factors of CSCC.Results The positive expression rate of ATG-12 protein in CSCC was 26.42%(28/106),lower than that in chronic cervicitis and CIN(P<0.05).The expression of ATG-12 protein was negatively correlated with the viral load of HPV 16-E6/E7-DNA(r=-0.306,P=0.001;r=-0.436,P=0.001).ATG-12 protein expression was related to FIGO stage,interstitial infiltration,lymphatic vessel space infiltration and lymph node metastasis(P<0.05).After 11-64 months follow-up,the 5-year tumor free survival rate was 78.57%(22/28)in patients with positive ATG-12 protein expression and 60.26%(47/78)in patients with negative ATG-12 protein expression.Multivariate Cox risk regression model analysis showed that HPV16-E6/E7-DNA viral load and ATG-12 protein expression were independent prognostic factors(P<0.05).Conclusion Positive expression rate of ATG-12 in early cervical squamous cell carcinoma is low,which is negatively correlated with HPV16-E6/E7-DNA viral load,and it is expected to be an important index to evaluate the prognosis of patients with HPV positive early cervical cancer.

关 键 词：宫颈鳞状上皮癌 癌前病变 HPV16-E6/E7-DNA病毒载量 ATG-12 预后 

分 类 号：R737.33[医药卫生—肿瘤]