子宫内膜癌组织中GATA结...附睾蛋白4的表达及临床意义_王晓娟.pdf

癌症进展2023 年 3 月第 21 卷第 5 期ONCOLOGY PROGRESS,Mar 2023 V ol.21,No.5*论著*子宫内膜癌组织中子宫内膜癌组织中GATAGATA结合蛋白结合蛋白3 3、人附睾蛋白人附睾蛋白4 4的表达的表达及临床意义及临床意义王晓娟#，董娜，徐鹏育河南科技大学临床医学院/河南科技大学第一附属医院病理科，河南 洛阳 4710000摘要摘要：目的目的探讨子宫内膜癌组织中人附睾蛋白4（HE4）、GATA结合蛋白3（GATA3）的表达及临床意义。方法方法将32例子宫内膜癌患者设为子宫内膜癌组，33例不典型增生患者设为不典型增生组，27例健康体检者设为正常对照组。统计3组受试者组织中HE4、GATA3阳性表达情况，分析GATA3、HE4阳性表达与子宫内膜癌患者临床特征的关系，计算HE4与GATA3单独及联合检测对子宫内膜癌的诊断效能。结果结果子宫内膜癌组患者HE4、GATA3阳性表达率均高于不典型增生组和正常对照组，不典型增生组患者HE4、GATA3阳性表达率均高于正常对照组，差异均有统计学意义（P0.05）。有淋巴结转移、肿瘤直径2 cm、组织学分级为G3级、有脉管浸润、手术-病理分期为+期子宫内膜癌患者子宫内膜癌组织中 HE4、GATA3 阳性表达率分别高于无淋巴结转移、肿瘤直径2 cm、组织学分级为G1+G2级、无脉管浸润、手术-病理分期为+期患者，差异均有统计学意义（P0.05）。有淋巴结转移、肿瘤直径2 cm、组织学分级为G3级、有脉管浸润、手术-病理分期为+期均为子宫内膜癌组织中HE4、GATA3阳性表达的危险因素（P0.05）。GATA3+HE4联合检测诊断子宫内膜癌的灵敏度高于GATA3单独检测，特异度高于HE4单独检测，阴性预测值和阳性预测值均高于GATA3和HE4单独检测。结论结论HE4在子宫内膜癌中高表达，GATA3呈中低水平表达，二者综合应用对子宫内膜癌的诊断价值更高，对早期子宫内膜癌分期诊断、靶向治疗及预后评估有指导意义。关键词关键词：子宫内膜癌；人附睾蛋白4；GATA结合蛋白3；临床特征；诊断价值中图分类号中图分类号：R R737737.3333文献标志码文献标志码：AdoiAdoi：10.11877/j.issn.1672-1535.2023.21.05.13Expression and clinical significance of GATAbinding proteinExpression and clinical significance of GATAbinding protein 3 3 and humanand humanepididymis proteinepididymis protein 4 4 in endometrial cancer tissuesin endometrial cancer tissuesWANG Xiaojuan#,DONG Na,XU PengyuDepartment of Pathology,School of Clinical Medicine,He nan University of Science and Technology/the First Affiliated Hospital ofHe nan University of Science and Technology,Luoyang 471000,He nan,ChinaAbstract:ObjectiveAbstract:ObjectiveTo investigate the expression and clinical significance of human epididymis protein 4(HE4)and GATA binding protein 3(GATA3)in endometrial cancer tissues.MethodMethodThirty-two patients with endometrial can-cer were set as the endometrial cancer group,33 patients with atypical hyperplasia were set as the atypical hyperplasiagroup,and 27 healthy subjects were set as the normal control group.The positive rates of HE4 and GATA3 in the tissuesof the three groups were counted.The relationship between the positive expression of GATA3 and HE4 and the clinicalcharacteristics of endometrial cancer patients were analyzed.The diagnostic efficiency of HE4 and GATA3 alone andcombined detection for endometrial cancer were also calculated.ResultResultThe positive expression rates of HE4 and GA-TA3 in the endometrial cancer group were higher than those in the atypical hyperplasia group and the normal controlgroup,the positive expression rates of HE4 and GATA3 in the atypical hyperplasia group were higher than those in thenormal control group,and the differences were statistically significant(P0.05).The positive expression rates of HE4 andGATA3 in endometrial cancer tissues of patients with lymph node metastasis,tumor diameter2 cm,histological gradeG3,vascular invasion,and surgical-pathological stage III+IV were higher than those without lymph node metastasis,tu-mor diameter2 cm,histological grade G1+G2,no vascular invasion,surgical-pathological stage I+II patients,and the dif-ferences were statistically significant(P0.05).Lymph node metastasis,tumor diameter2 cm,histological grade G3,vas-cular invasion,and surgical-pathological stage III+IV were all risk factors for positive expression of HE4 and GATA3 inendometrial cancer tissues(P0.05).The sensitivity of GATA3+HE4 combined detection in the diagnosis of endometrialcancer was higher than that of GATA3 alone,the specificity was higher than that of HE4 alone,the negative predictivevalue and positive predictive value were higher than those of GATA3 and HE4 alone.ConclusionConclusionHE4 is up-regulationin endometrial cancer,and GATA3 is at low to medium levels.The combined application of the two indicators couldachieve higher diagnostic value for endometrial cancer,and guide stage diagnosis,targeted therapy,and prognosis evalua-tion of early endometrial cancer.#通信作者（corresponding author），邮箱：517癌症进展2023年3月第21卷第5期Key words:Key words:endometrial cancer;human epididymis protein 4;GATA binding protein 3;clinical characteristic;diag-nostic valueOncol Prog,2023,21(5)子宫内膜癌是发生于子宫内膜的一组上皮性恶性肿瘤，占女性全身恶性肿瘤的 7%，近年来发病率在世界范围内呈上升趋势，若疾病发现较晚，可出现贫血、消瘦及恶病质等相应症状，导致预后不良1-2。a期和b期子宫内膜癌采用的手术方式不同，因此术前准确判断早期子宫内膜癌的分期有助于治疗方案的决策。诊断性刮宫和宫腔镜下活检虽可检出病变性质，但在评估分期方面仍然存在局限3-4。因此，有学者指出可将血清生物标志物纳入术前风险评估。人附睾蛋白4（humanepididymis protein 4，HE4）是一种分泌型糖蛋白，在子宫内膜癌中呈高水平表达。HE4受良性妇科疾病的影响较小，具有追踪预后的潜力5-6，但仅凭该标志物诊断，特异度不佳。研究指出，转录因子 GATA 结合蛋白 3（GATA binding protein 3，GA-TA3）对乳腺和尿路上皮起源的肿瘤具有较高的敏感性，在乳腺癌中阳性表达率高达94%，在尿路上皮癌中为 86%7-8。基于此，本研究探讨 HE4、GA-TA3在子宫内膜癌患者及其他人群组织中的表达水平，以进一步评估以上标志物在早期子宫内膜癌诊断中的价值，现报道如下。1 1资料与方法资料与方法1 1.1 1 一般资料一般资料收集2018年5月至2020年5月河南科技大学第一附属医院收治的子宫内膜癌患者、不典型增生患者的病历资料。纳入标准：经病理检查确诊；精神状态良好；未行手术或化疗；病历资料完整。排除标准：拒绝采血等操作；随访资料不完整或不真实。根据纳入、排除标准，共纳入32例子宫内膜癌患者（设为子宫内膜癌组）、33例不典型增生患者（设为不典型增生组）。另选取同期27例健康体检者设为正常对照组。子宫内膜癌组患者年龄3067岁，平均（47.925.16）岁；不典型增生组患者年龄3166岁，平均（46.895.31）岁；正常对照组年龄2965岁，平均（47.434.92）岁。3组受试者年龄比较，差异无统计学意义（P0.05），具有可比性。本研究经医院伦理委员会批准通过，所有患者均知情同意。1 1.2 2 检测方法检测方法使用鼠抗人 GATA3 单克隆抗体、鼠抗人 HE4单克隆抗体进行免疫组化染色：每例标本切取3张切片，每张厚度切至 3 m 左右，并脱蜡水化。于3%过氧化氢溶液中室温孵育10 min，蒸馏水冲洗，采用0.01 mmol/