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中华乳腺病杂志(电子版) ›› 2020, Vol. 14 ›› Issue (01) : 32 -36. doi: 10.3877/cma.j.issn.1674-0807.2020.01.009

所属专题: 文献

论著

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
张光君1, 王唯依2, 黄雨3, 涂刚1,()   
  1. 1. 400016 重庆医科大学附属第一医院内分泌乳腺外科
    2. 116000 解放军联勤保障部队大连康复疗养中心
    3. 322099 浙江省义乌市妇幼保健院乳腺外科
  • 收稿日期:2019-11-14 出版日期:2020-02-01
  • 通信作者: 涂刚

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

Guangjun Zhang1, Weiyi Wang2, Yu Huang3, Gang Tu1,()   

  1. 1. Department of Endocrine and Breast Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
    2. Dalian Rehabilitation and Recuperation Center of PLA Joint Logistic Support Force, Dalian 116000, China
    3. Department of Breast Surgery, Yiwu Maternal and Child Health Hospital, Yiwu 322099, China
  • Received:2019-11-14 Published:2020-02-01
  • Corresponding author: Gang Tu
  • About author:
    Corresponding author: Tu Gang, Email:
引用本文:

张光君, 王唯依, 黄雨, 涂刚. 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[J]. 中华乳腺病杂志(电子版), 2020, 14(01): 32-36.

Guangjun Zhang, Weiyi Wang, Yu Huang, Gang Tu. Relationship between G-protein coupled estrogen receptor mRNA expression and clinicopathologic characteristics and prognosis of breast cancer patients[J]. Chinese Journal of Breast Disease(Electronic Edition), 2020, 14(01): 32-36.

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(P25P75 )]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。

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 (P25-P75)]. GPER mRNA expression in 1 085 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 3 951 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 6.247 9(6.022 4-6.554 6) in normal breast tissue and 5.700 4(5.357 6-6.022 0) 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 (χ2=3.343, 6.084; P=0.488, 0.193). The expression of GPER mRNA was -0.239 3 (-0.250 7--0.126 1), -0.263 9 (-0.275 9--0.225 7) and -0.188 3 (-0.239 7--0.101 9) in basal-like, HER-2, and luminal subtypes, suggesting a significant difference (χ2=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.

图1 GPER mRNA在乳腺癌组织与癌旁正常组织中表达的差异
表1 乳腺癌临床病理特征与GPER mRNA表达的关系
图2 不同GPER mRNA表达的乳腺癌患者无复发生存曲线
[1]
郑荣寿,孙可馨,张思维,等.2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019,41(1): 19-28.
[2]
Hall JM, Couse JF, Korach KS. The multifaceted mechanisms of estradiol and estrogen receptor signaling [J]. J Biol Chem, 2001, 276(40): 36 869-36 872.
[3]
Carmeci C, Thompson DA, Ring HZ. Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer[J]. Genomics, 1997, 45(3): 607-617.
[4]
Revankar CM, Cimino DF, Sklar LA, et al. A transmembrane intracellular estrogen receptor mediates rapid cell signaling [J]. Science, 2005, 307(5715): 1625-1630.
[5]
Thomas P, Pang Y, Filardo EJ, et al. Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells[J]. Endocrinology, 2005, 146(2): 624-632.
[6]
Filardo E, Quinn J, Pang Y, et al. Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane[J]. Endocrinology, 2007, 148(7): 3236-3245.
[7]
Albanito L, Madeo A, Lappano R, et al. G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells[J]. Cancer Res, 2007, 67(4): 1859-1866.
[8]
Pupo M, Pisano A, Lappano R, et al. Bisphenol A induces gene expression changes and proliferative effects through GPER in breast cancer cells and cancer-associated fibroblasts[J]. Environ Health Perspect, 2012, 120(8): 1177-1182.
[9]
Yu T, Liu M, Luo H, et al. GPER mediates enhanced cell viability and motility via non-genomic signaling induced by 17beta-estradiol in triple-negative breast cancer cells[J]. J Steroid Biochem Mol Biol, 2014, 143: 392-403.
[10]
Martin SG, Lebot MN, Sukkarn B, et al. Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients[J]. Oncotarget, 2018, 9(40): 25 946-25 956.
[11]
Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 45(W1):W98-102.
[12]
Gyorffy B, Lanczky A, Eklund AC, et al. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1809 patients[J]. Breast Cancer Res Treat, 2010,123(3):725-731.
[13]
Filardo EJ, Quinn JA, Bland KI, et al, Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF[J]. Mol Endocrinol, 2000, 14(10): 1649-1660.
[14]
Ignatov T, Modl S, Thulig M, et al. GPER-1 acts as a tumor suppressor in ovarian cancer[J]. J Ovarian Res, 2013, 6(1): 51.
[15]
Tsai CL, Wu HM, Lin CY, et al. Estradiol and tamoxifen induce cell migration through GPR30 and activation of focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear estrogen receptor alpha (ERalpha) [J]. PLoS One, 2013, 8(9): e72999.
[16]
Poola I, Abrham J, Liu A, et al. The cell surface estrogen receptor, G protein-coupled receptor 30 (GPR30), is markedly down regulated during breast tumorigenesis[J]. Breast Cancer (Auckl), 2008,1: 65-78.
[17]
Pandey DP, Lappano R, Albanito L, et al. Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF[J]. EMBO J, 2009, 28(5): 523-532.
[18]
Li Y, Chen Y, Zhu ZX, et al. 4-hydroxytamoxifen-stimulated processing of cyclin E is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells[J]. Toxicology, 2013,309: 61-65.
[19]
Pupo M, Pisano A, Abonante S, et al. GPER activates Notch signaling in breast cancer cells and cancer-associated fibroblasts (CAFs) [J]. Int J Biochem Cell Biol, 2014,46: 56-67.
[20]
Jiang QF, Wu TT, Yang JY, et al. 17beta-estradiol promotes the invasion and migration of nuclear estrogen receptor-negative breast cancer cells through cross-talk between GPER1 and CXCR1[J]. J Steroid Biochem Mol Biol, 2013, 138: 314-324.
[21]
Mo Z, Liu M, Yang F, et al. GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer[J]. Breast Cancer Res, 2013,15(6): R114.
[22]
郭林英,余腾骅,张光君,等. 肿瘤相关成纤维细胞中GPER介导HMGB1外分泌促进乳腺癌MCF-7细胞自噬及增殖[J].肿瘤, 2017, 37(5):448-456.
[23]
余腾骅,涂刚,彭美茜,等. 肿瘤相关成纤维细胞中G蛋白偶联雌激素受体胞浆转位介导的旁分泌对乳腺癌细胞生长的影响[J].中国普通外科杂志, 2019,28(5):573-580.
[24]
Santolla MF, Vivacqua A, Lappano R, et al. GPER mediates a feedforward FGF2/FGFR1 paracrine activation coupling CAFs to cancer cells toward breast tumor progression[J]. Cells, 2019,8(3): E223.
[25]
Weißenborn C, Ignatov T, Poehlmann A, et al, GPER functions as a tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells[J]. J Cancer Res Clin Oncol, 2014, 140(4): 663-671.
[26]
Ignatov A, Ignatov T, Weissenborn C, et al. G-protein-coupled estrogen receptor GPR30 and tamoxifen resistance in breast cancer[J]. Breast Cancer Res Treat, 2011, 128(2):457-466.
[27]
Sjöström M, Hartman L, Grabau D, et al. Lack of G protein-coupled estrogen receptor (GPER) in the plasma membrane is associated with excellent long-term prognosis in breast cancer[J]. Breast Cancer Res Treat, 2014,145(1):61-71.
[28]
Broselid S, Cheng B, Sjöström M, et al. G protein-coupled estrogen receptor is apoptotic and correlates with increased distant disease-free survival of estrogen receptor-positive breast cancer patients[J]. Clin Cancer Res, 2013,19(7): 1681-1692.
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