摘要
目的:探索免疫检查点人内源性逆转录病毒-H长末端重复关联蛋白2(HHLA2)在子宫内膜癌中的表达及临床意义。方法:回顾性收集192例子宫内膜癌患者的组织标本及临床病理资料,利用Sanger测序检测POLE突变,免疫组化染色检测错配修复蛋白及p53蛋白表达。将子宫内膜癌划分为POLE突变型、错配修复缺陷型(MMRd)、p53突变型及无特定分子特征(NSMP)型,免疫组化染色检测HHLA2蛋白表达,利用卡方检验分析HHLA2蛋白与临床病理特征及分子分型的关系。采用Kaplan-Meier法和Cox比例风险回归模型分析影响子宫内膜癌患者预后的相关因素。结果:HHLA2蛋白在子宫内膜癌中的阳性表达率为69.8%(134/192)。子宫内膜样癌、中-高分化肿瘤、I期、浅肌层浸润、无淋巴脉管间隙浸润及分子分型为NSMP型的肿瘤中HHLA2蛋白表达率较高。整个研究队列及分子分型为NSMP型的亚组患者中,HHLA2蛋白表达阳性患者的无疾病复发生存率高于HHLA2蛋白表达阴性患者(P<0.05)。多因素生存分析显示,分子分型是子宫内膜癌患者的预后因素(P<0.05)。结论:HHLA2是NSMP型子宫内膜癌的预后因素和潜在治疗靶点。
Objective:To explore the expression and clinical significance of the immune checkpoint human endogenous retrovirus-H long terminal repeat-associating protein 2(HHLA2)in endometrial cancer.Methods:Tissue samples and clinicopathological data of 192 patients with endometrial cancer were retrospectively collected,and POLE was detected by Sanger sequencing and the expression of mismatch repair protein and p53 protein was detected by immunohistochemical staining,and endometrial cancer was divided into POLE mutant,mismatch repair defective(MMRd),p53 mutant and no specific molecular feature(NSMP)type.The expression of HHLA2 protein was detected by immunohistochemical staining.The Chi-square test was used to analyze the relationship between HHLA2 protein and clinicopathological features and molecular type.The Kaplan-Meier method and Cox proportional hazards regression model were used to analyze the relevant factors affecting the prognosis of patients with endometrial cancer.Results:The positive rate of HHLA2 protein in endometrial carcinoma was 69.8%(134/192),and it was higher in endometrioid endometrial carcinoma,intermediate-well differentiated tumor,stage I,superficial muscular invasion,without lymphovascular space invasion and NSMP type tumor.Across the study cohort and in the subgroup of patients with molecular type NSMP,patients with HHLA2-positive tumor had improved recurrence-free survival than those with HHLA2-negative tumor(P<0.05).Multivariate survival analysis showed that molecular typing was a prognostic factor in patients with endometrial cancer(P<0.05).Conclusions:HHLA2 is a prognostic factor and potential therapeutic target for endometrial cancer with molecular type NSMP.
作者
王颉
常惠婷
黄守国
Wang Jie;Chang Huiting;Huang Shouguo(Department of Obstetrics and Gynecology,Central South University Xiangya School of Medicine Affiliated Haikou Hospital,Haikou 570208)
出处
《现代妇产科进展》
北大核心
2023年第8期566-570,共5页
Progress in Obstetrics and Gynecology
关键词
子宫内膜癌
免疫检查点
人内源性逆转录病毒-H长末端重复关联蛋白2
分子分型
预后
Endometrial carcinoma
Immune checkpoint
Human endogenous retrovirus-H long terminal repeat-associating protein 2
Molecular classification
Prognosis
