利用TCGA数据库分析促性腺激素释放激素及其受体在乳腺癌中的表达及临床意义

Analysis of clinical significance of gonadotropin-releasing hormone and its receptor in breast cancer utilizing TCGA database

目的研究促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)及其受体(gonadotropin-releasing hormone receptor,GnRHR)在乳腺癌中的表达情况,探索其临床意义。方法从美国癌症基因组图谱(The Cancer Genomes Atlas,TCGA)数据库下载乳腺癌患者GnRH、GnRHR基因表达数据和临床病理信息资料,分析GnRH、GnRHR与乳腺癌临床病理学指标和预后的相关性。结果乳腺癌组织中GnRH表达量低于正常乳腺组织(0.42 vs 1.27,P=0.000),其与年龄(U=134190.000,P=0.046)、人种(χ2=30.030,P=0.000)、淋巴结状态(U=126697.000,P=0.003)、ER(U=69435.000,P=0.000)、PR(U=99978.000,P=0.000)、HER2(U=53388,P=0.000)相关,以年龄≤55岁、黑人或非裔美国人、淋巴结阴性、ER阴性、PR阴性、HER2阴性者GnRH表达量较高。生存分析提示GnRH高表达组总生存期(overall survival,OS)优于低表达组(P=0.018)。乳腺癌组织中GnRHR表达量与正常乳腺组织相似(0.08 vs 0.07,P=0.778),其与年龄(U=133325.000,P=0.031)、人种(χ2=16.829,P=0.000)、ER(U=68438.000,P=0.000)、PR(U=92714.500,P=0.000)、HER2(U=66205.000,P=0.030)相关,以年龄>55岁、白人、ER阳性、PR阳性、HER2阴性者GnRHR表达量较高。GnRHR高表达组与低表达组间OS差异无统计学意义(P=0.719),亚组分析发现在三阴性乳腺癌亚组中GnRHR高表达组OS优于低表达组(P=0.028),而在非三阴性亚组中GnRHR与OS无相关性(P=0.976)。结论GnRH、GnRHR表达与乳腺癌部分临床病理学指标存在相关性,与乳腺癌(尤其是三阴性乳腺癌)的预后存在相关性。GnRH、GnRHR信号通路可能具有抑癌活性。

Objective To investigate the clinical significance of gonadotropin-releasing hormone(GnRH)and its receptor(GnRHR)expression in breast cancer.Methods GnRH and GnRHR expression data in The Cancer Genomes Atlas(TCGA)database and its clinical information were downloaded.Statistically assessed was performed for relationship with clinicopathological factors and prognosis.Results The expression of GnRH in breast cancer tissues was lower than that in normal breast tissue(0.42 vs 1.27,P=0.000),and it was correlated with age(P=0.046),race(P=0.000),lymphnode status(P=0.003),ER(P=0.000),PR(P=0.000),and HER2(P=0.000).The GnRH expression was higher in patients whose age≤55 years,black or African American,lymphnode negative,ER negative,PR negative,and HER2 negative.Survival analysis suggested that the Overall Survival(OS)in GnRH high expression group was better than in low expression group(P=0.018).The expression of GnRHR in breast cancer tissues was similar to normal breast tissue(0.08 vs 0.07,P=0.778),and it was correlated with age(P=0.031),race(P=0.000),ER(P=0.000),PR(P=0.000),and HER2(P=0.030).The GnRHR expression was higher in patients whose age>55 years,white,ER positive,PR positive,and HER2 negative.There was no significant difference in OS between GnRHR high expression group and low expression group(P=0.719).Subgroup analysis showed that OS in GnRHR high expression group was better than in low expression group(P=0.028)in the triple negative breast cancer subgroup,while GnRHR was not associated with OS in the non-triple negative subgroup(P=0.976).Conclusion The expressions of GnRH and GnRHR are correlated with some clinicopathological parameters of breast cancer,and the prognosis of oreast cancer(especially triple negative breast cancer).The GnRH and GnRHR signaling pathways maybe have tumor suppressor activity.