G蛋白偶联雌激素受体mRNA表达与乳腺癌患者临床病理特征及预后的关系

目的基于癌症和肿瘤基因图谱(TCGA)和Kaplan-Meier Plotter数据库探讨G蛋白偶联雌激素受体(GPER)mRNA在乳腺癌组织中的表达及其与预后的关系。 方法本回顾性研究利用基因表达谱交互分析(GEPIA)工具下载含有乳腺癌患者GPER mRNA二代测序数据及临床病理资料的TCGA数据集,GPER mRNA表达为偏态分布数据,用[M(P₂₅ ～P₇₅ )]表示,采用Wilcoxon W检验分析1 085例乳腺癌组织样本和291例正常乳腺组织样本GPER mRNA表达的差异,同时用Kruskal-Wallis H检验分析乳腺癌组织中GPER mRNA表达与其临床病理特征的关系,两两比较用Bonferroni-Dunn检验。利用Kaplan-Meier Plotter数据库收集共3 951例乳腺癌患者的GPER mRNA表达情况,根据GPER mRNA表达的上下四分位数确定最佳截点值(103),从而将其分为GPER高、低表达2组,进而绘制无复发生存曲线,使用log-rank检验比较GPER高表达与低表达组的无复发生存率差异。 结果正常乳腺组织中GPER mRNA表达为6.247 9(6.022 4～6.554 6),乳腺癌组织中为5.700 4(5.357 6～6.022 0),差异有统计学意义(Z＝－7.338,P<0.001)。不同T分期、N分期的乳腺癌组织中GPER mRNA表达比较,差异无统计学意义(χ²＝3.343、6.084,P＝0.488、0.193)。GPER mRNA在basal-like型、HER-2型、luminal型中的表达分别为－0.239 3(－0.250 7～－0.126 1)、－0.263 9(－0.275 9～－0.225 7)、－0.188 3(－0.239 7～－0.101 9),差异有统计学意义(χ²＝106.187, P<0.001)。两两比较发现,HER-2型与basal-like型、HER-2型与luminal型、basal-like型与luminal型相比,GPER mRNA表达的差异均有统计学意义(P＝0.019,P均<0.001)。GPER mRNA低表达患者的无复发生存率明显低于高表达患者(HR＝0.67,95%CI：0.59～0.75,P<0.001)。 结论GPER mRNA低表达患者预后更差,提示GPER可能成为乳腺癌患者预后的独立预测因子。

Relationship between G-protein coupled estrogen receptor mRNA expression and clinicopathologic characteristics and prognosis of breast cancer patients

Objective To investigate the expression of G-protein coupled estrogen receptor(GPER)mRNA in breast cancer based on the Cancer Genome Atlas(TCGA)and Kaplan-Meier Plotter databases and its relationship with patient prognosis.Methods This retrospective study used the Gene Expression Profiling Interactive Analysis(GEPIA)to download a TCGA dataset containing next-generation sequence of GPER mRNA and clinicopathological data of breast cancer patients.Because of skewed data distribution,GPER mRNA was expressed as[M(P 25-P 75)].GPER mRNA expression in 1085 cases of breast cancer tissue samples and 291 cases of normal breast tissue was compared using Wilcoxon W test.The relationship between GPER mRNA expression in breast cancer tissue and clinicopathological characteristics was analyzed using the Kruskal-Wallis H test and Bonferroni-Dunn test was used for pairwise comparison.The GPER mRNA expression in 3951 breast cancer patients from the Kaplan-Meier Plotter database was analyzed.The optimal cutoff value(103)was determined according to the upper and lower quartiles of GPER mRNA expression,so that the patients were divided into high and low GPER expression groups,and then the recurrence-free survival curve was drawn.The log-rank test was used to compare the recurrence-free survivals between patients with high GPER expression and patients with low GPER expression.Results The expression of GPER mRNA was 6.2479(6.0224-6.5546)in normal breast tissue and 5.7004(5.3576-6.0220)in breast cancer tissue,indicating a significant difference(Z=-7.338,P<0.001).There was no significant difference in GPER mRNA expression among breast cancer patients with different T stage and N stage(χ^2=3.343,6.084;P=0.488,0.193).The expression of GPER mRNA was-0.2393(-0.2507--0.1261),-0.2639(-0.2759--0.2257)and-0.1883(-0.2397--0.1019)in basal-like,HER-2,and luminal subtypes,suggesting a significant difference(χ^2=106.187,P<0.001).Pairwise comparison showed that GPER mRNA expression presented a significant difference between HER-2 and basal-like subtypes(P=0.019),HER-2 and luminal subtypes(P<0.001),basal-like and luminal subtypes(P<0.001).The recurrence-free survival in patients with low GPER mRNA expression was significantly lower than that in patients with high expression(HR=0.67,95%CI:0.59-0.75,P<0.001).Conclusion The patients with low GPER mRNA expression have a poor prognosis,suggesting that GPER may be a potential independent factor to predict the prognosis of breast cancer patients.