子宫内膜样腺癌中PLAGL1和ERβ的表达及临床意义

Expression of PLAGL1 and ERβin uterine endometrioid adenocarcinoma and its clinical significance

目的探讨多形性腺瘤基因L1(pleomorphic adenoma gene like-1,PLAGL1)和雌激素受体(estrogen receptorβ,ERβ)在子宫内膜样腺癌(uterine endometrioid adenocarcinoma,UTEA)中的表达及两者与临床病理特征的关系。方法筛选肿瘤基因组图谱(the Cancer Genome Atlas,TCGA)中子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)及正常子宫内膜组织中的差异表达基因;采用UALCAN数据库分析PLAGL1和ESR2 mRNA在UCEC及正常组织中的表达。采用免疫组化法检测84例UTEA及43例癌旁正常子宫内膜中PLAGL1和ERβ表达,分析两者与UTEA临床病理特征的关系及相关性。结果TCGA及UALCAN数据库分析显示:UCEC中PLAGL1 mRNA表达显著低于正常子宫内膜组织(P<0.01),而正常子宫内膜组织和UCEC中ESR2 mRNA的表达水平差异无统计学意义(P>0.05)。UTEA中PLAGL1高表达率为34.5%,显著低于正常组织(74.4%,P<0.01);ERβ高表达率为39.3%,与正常组织差异无显著性(34.9%,P>0.05);UTEA中PLAGL1与ERβ表达呈正相关(r=0.236,P<0.05)。UTEA中PLAGL1表达与组织学分级、临床分期、肿瘤累及子宫颈、肌层浸润深度、淋巴结转移和p53错义突变均显著相关(P均<0.05),与患者年龄及绝经状态无关(P均>0.05);ERβ表达与患者年龄、绝经状态、组织学分级、临床分期、肿瘤累及子宫颈、肌层浸润深度、淋巴结转移和p53错义突变均无关(P均>0.05)。结论UTEA中PLAGL1蛋白表达显著降低,PLAGL1和ERβ异常表达可能联合参与UTEA的发生、发展。

Purpose To investigate the expression of pleomorphic adenoma gene like-1(PLAGL1)and ERβproteins in uterine endometrioid adenocarcinoma(UTEA)and its relationship with clinicopathological characteristics.Methods Differentially expressed genes in uterine corpus endometrial carcinoma(UCEC)and normal endometrium tissues from TCGA database were screened.The expression of PLAGL1 and ESR2 mRNAs in UCEC and normal endometrium tissues in UALCAN database was analyzed.84 paraffin samples from UTEA and 43 paraffin samples from paracancer normal endometrium tissues were collected.The expression of PLAGL1 and ERβproteins from paraffin samples was detected by immunohistochemistry,and the relationship between the expression level of PLAGL1 and ERβproteins and clinicopathological characteristics of UTEA patients was analyzed.Results Data from TCGA and UALCAN databases suggested that the expression of PLAGL1 mRNA in UCEC tissues was significantly lower than that in normal endometrium tissues(P<0.01),while the expression of ESR2 mRNA in those tissues was no significant difference(P>0.05).In UTEA,the high expression rate of PLAGL1 was 34.5%,which was significantly lower than that in adjacent tissues(74.4%,P<0.01).The high expression rate of ERβwas 39.3%,which showed no significant difference with paracancer tissue(34.9%,P>0.05).PLAGL1 protein expression was positively correlated with ERβin UTEA(r=0.236,P<0.05).The expression of PLAGL1 protein in UTEA was significantly correlated with tumor grade,clinical stage,cervical involvement,invasion depth,lymph node metastasis and p53 missense mutation(all P<0.05),but not to the age and menopausal status(both P>0.05).The expression of ERβprotein was no significantly correlated with age,menopausal status,tumor grade,clinical stage,cervical involvement,invasion depth,lymph node metastasis and p53 missense mutation(all P>0.05).Conclusion PLAGL1 protein expression level in UTEA is significantly decreased.The abnormal expression of PLAGL1 and ERβmay be involved in the development and progression of UTEA.