宫颈鳞状细胞癌中染色体结构...表达变化及与临床预后的关系_高婷婷.pdf

山西医药杂志 2023 年 4 月第 52 卷第 8 期Shanxi Med J，April 2023，Vol.52.No.8宫颈鳞状细胞癌中染色体结构维持蛋白 4细胞毒性 T 细胞相关抗原 4 表达变化及与临床预后的关系高婷婷王兆林师增增李雪峰潘珍妮王丽【摘要】目的分析染色体结构维持蛋白 4(SMC4)、细胞毒性 T 细胞相关抗原 4(CTLA4)表达变化与宫颈鳞状细胞癌临床病理参数及预后的相关性。方法选择 2016 年 8 月至 2017 年 8 月于我院收治宫颈鳞状细胞癌患者 56 例为观察组，同期选择于我院检查的健康人群 35 名为对照组，免疫组织化学检测 2 组病理组织SMC4、CTLA4 表达情况，采集并比较 2 组患者临床资料。采用多因素 Logisitic 回归分析影响宫颈鳞状细胞癌病发患者的危险因素，Kaplan-Meier 生存曲线分析 SMC4、CTLA4 表达在宫颈鳞状细胞癌预后的关系。采用受试者工作特征曲线(ROC 曲线)分析 SMC4、CTLA4 指标的曲线下面积(AUC)、灵敏度、特异度。结果相较于对照组，观察组宫颈组织 SMC4、CTLA4 表达评分明显升高，同时观察组流产、绝经、首次性交年龄小、首次生育年龄小、孕次多比例明显升高(P0.05)。多因素 Logisitic 回归分析发现，SMC4 高表达、CTLA4 高表达、流产、绝经、首次性交年龄小、首次生育年龄小、孕次多均为影响宫颈鳞状细胞癌病发危险因素(P0.05)。Kaplan-Meier生存分析结果显示，56 例宫颈鳞状细胞癌患者平均随访时间为 34 个月，高表达 SMC4(2.45，26 例)患者总生存期明显低于低表达 SMC4(30 例)患者，高表达 CTLA4(2.39，28 例)患者总生存期明显低于低表达 CTLA4(28例)患者(P0.05)。ROC 曲线分析发现，SMC4、CTLA4 诊断宫颈鳞状细胞癌的 AUC 为 0.723、0.725，两者联合诊断宫颈鳞状细胞癌的 AUC 为 0.854。结论SMC4、CTLA4 对预测宫颈鳞状细胞癌治疗预后具有一定的价值，患者 SMC4、CTLA4 水平升高提示预后不良风险较高，有望作为宫颈鳞状细胞癌的早期诊断生物学标志物。【关键词】癌，鳞状细胞；宫颈肿瘤；染色体结构维持蛋白 4；细胞毒 T 细胞分子 4；临床预后DOI：10.3969/j.issn.0253-9926.2023.08.007作者单位：710038 西安，空军军医大学唐都医院妇产科(高婷婷、王兆林、师增增、李雪峰、潘珍妮)；西安医学院附属第一医院产科(王丽)通信作者：潘珍妮，Email：Expression of SMC4 and CTLA4 in cervical squamous cell carcinoma and their relationship with clinicalprognosisGao Tingting*,Wang Zhaolin,Shi Zengzeng,Li Xuefeng,Liang Li,Wang Li.*Department of Obstetricsand Gynecology,Tangdu Hospital,Air Force Military Medical University,Xian 710038，China【Abstract】ObjectiveTo analyze the correlation between the expression of chromosome structuremaintenance protein 4(SMC4)and cytotoxic T lymphocyte associated antigen 4(CTLA4)and the clinicopathologicparameters and prognosis of cervical squamous cell carcinoma.MethodsFifty-six patients with cervical squamouscell carcinoma admitted to our hospital from August 2016 to August 2017 were selected as the observation group,and 35 healthy people examined in our hospital were selected as the control group at the same time.The expressionof SMC4 and CTLA4 in the pathological tissues of the two groups were detected by immunohistochemistry,and theclinical data of the two groups were collected and compared.Multivariate Logistic regression analysis was used toanalyze the risk factors affecting the occurrence of cervical squamous cell carcinoma.Kaplan-Meier survival curvewas used to analyze the relationship between the expression of SMC4 and CTLA4 in the prognosis of cervicalsquamous cell carcinoma.The area under curve(AUC),sensitivity and specificity of each SMC4 and CTLA4 indexwere analyzed using the subject operating characteristic curve(ROC curve).ResultsCompared with the controlgroup,the expression score of SMC4 and CTLA4 in the cervical tissue of the observation group was significantlyhigher,while the proportion of abortion,menopause,first sexual intercourse,first birth,multiple pregnancies in theobservation group were significantly higher(P70 岁。同期选择于我院检查的健康人群 35 名为对照组。本实验步骤均经我院伦理委员会批准同意。12观察指标临床资料：收集患者临床病例特征，包括年龄、民族、婚姻状态等一般资料及 SMC4 和 CTLA4 表达资料。1.3免疫组织化学取各组受检者宫颈组织标本，10%甲醛固定后石蜡包埋，制成石蜡切片，厚度为 4 m，恒温箱烤片 30 min，切片抗原修复，磷酸盐缓冲液(PBS)冲洗3 次，3%过氧化氢滴加于切片中，室温下孵育 15min，PBS 清洗 3 次，山羊血清封闭 30 min，滴加一抗 4 恒温箱中孵育 15 h，PBS 冲洗 3 次，滴加二抗室温孵育 20 min，二氨基联苯胺(DAB)显色苏木素复染 1 min，1%盐酸酒精分化，PBS 水洗反蓝，脱水透明后封胶，显微镜下观察各组宫颈组织着色强度。高倍视野均值取值：不着色为 0 分，黄色为 1分，棕黄色为 2 分，黄褐色为 3 分，阳性细胞率计分：0 分为阳性细胞5%，1 分为 6%阳性细胞25%；2 分为 26%阳性细胞50%；3 分为 51%76%。两种积分之和阴性为 01 分，弱阳性为 2 分，阳性为 34 分，强阳性为 5 分以上。14统计学方法采用 SPSS 200 软件对本研究数据进行分析。计量资料以 xs 表示，比较采用 t 检验；计数资料以例(%)表示，比较采用 2检验。影响宫颈鳞状细胞癌病发患者影响采用多因素 Logisitic 回归分析。Kaplan-Meier 生存曲线分析 SMC4、CTLA4 表达在pression of SMC4,high expression of CTLA4,abortion,menopause,small age of first sexual intercourse,small age offirst birth,multiple pregnancies were all risk factors for cervical squamous cell carcinoma(P0.05).Kaplan-Meiersurvival analysis showed that the average follow-up time of 56 patients with cervical squamous cell carcinoma was34 months.The total survival time of patients with high expression of SMC4(2.45,n=26)was significantly lowerthan that of patients with low expression of SMC4(n=30),and that of patients with high expression of CTLA4(2.39,n=28)was significantly lower than that of patients with low expression of CTLA4(n=28)(P0.05).ROC curve anal-ysis showed that the AUC of SMC4 and CTLA4 in the diagnosis of cervical squamous cell carcinoma was 0.723 and0.725,and the AUC of both in the diagnosis of cervical squamous cell carcinoma was 0.854.ConclusionSMC4and CTLA4 are of certain value in predicting the treatment prognosis of cervical squamous cell carcinoma.The ele-vated levels of SMC4 and CTLA4 in patients suggest a high risk of poor prognosis.It is expected to be used as bio-logical markers for early diagnosis of cervical squamous cell carcinoma.【Key words】Carcinoma,squamous cell;Uterine cervical neoplasms;Chromosome structure maintenanceprotein 4;Cytotoxic T cell molecule 4;Clinical prognosis593山西医药杂志 2023 年 4 月第 52 卷第 8 期Shanxi Med J，April 2023，Vol.52.No.8SMC4CTLA4082120002800034528920.370412242（1055，4810）3321（1502，7351）因素值sxWald 2值P值OR值（95CI）表 2影响宫颈鳞状