Expression Of The Novel G Protein-coupled Estrogen Receptor 1(GPER1)in Lung Adenocarcinoma And Mediates Proliferation Of Lung Cancer Cells

Objective:To analyze the expression of the novel estrogen receptor GPER1 in lung adenocarcinoma tissues and cells,to analyze the correlation among GPER1,ERα and ERβ expression,to elucidate the relationship between GPER1,ERa and ERβ and clinicopathological features,and further explore the role of GPER1 in mediating lung cancer cell proliferation.Methods:Immunohistochemistry(IHC)was used to detect the expression and location of GPER1,ERa and ERβ in 53 cases of paraffin-embedded tissues of lung adenocarcinoma diagnosed by pathologically confirmed thoracic surgery in Yan’an Hospital Affiliated to Kunming Medical University from 2016 to 2018;The relationship between the positive expression of GPER1,ERα and ERβ and clinicopathological features was analyzed by paired chi-square test;The correlation among GPER1,ERa and ERβ were analyzed by Spearman rank correlation test;Further,semi-quantitative PCR was used to detect the expression of GPER1,ERα and ERβ in lung adenocarcinoma PC-9 cells at mRNA level;The effect of GPER1 on the proliferation of lung adenocarcinoma PC-9 cells was detected by Cell Counting Kit-8 assay(CCK-8).Results:1.In human lung adenocarcinoma tissues,the positive expression rate of GPER1 was 30.19%(16/53),ERa was 52.83%(28/53),ERβ was 39.62%(21/53),and positive expression of GPER1,ERa and ERβ were localized in the cytoplasm.2.The positive rate of GPER1 in patients with lymph node metastasis was 50.00%(9/18),and the positive rate of GPER1 in patients without lymph node metastasis was 20.00%(7/35)(P<0.05);The positive rate of GPER1 in patients with III-IV lung adenocarcinoma was 55.60%(10/18),and the positive rate of GPER1 in patients with stage Ⅰ-Ⅱ lung adenocarcinoma was 17.10%(6/35)(P<0.05);There was no significant difference between GPER1 expression and age,sex,degree of differentiation and tumor size in patients with lung adenocarcinoma(P>0.05).In addition,although there was no statistically significant age(P=0.059),the positive expression rate was higher in the≥60-year old group than in the<60-year old group(42.30%vs.18.50%).3.The positive rate of ERa in patients with lymph node metastasis was 72.20%(13/18),and the positive rate of ERa in patients without lymph node metastasis was 42.90%(15/35)(P<0.05);The positive rate of ERa in patients with III-IV lung adenocarcinoma was 77.80%(14/18),and the positive rate of ERa in patients with stage Ⅰ-Ⅱ lung adenocarcinoma was 40.00%(14/35)(P<0.05);There was no significant difference in age,sex,degree of differentiation and tumor size in lung adenocarcinoma patients between ERa expression(P>0.05).4.There was no significant difference in ERβ expression between age,sex,lymph node metastasis,TNM stage,degree of differentiation and tumor size(P>0.05).5.Estrogen receptors GPER1,ERα and ERβ showed a low positive correlation(GPER1 and ERa,r=0.457,P=0.001;GPER1 and ERβ,r=0.476,P<0.001;ERa and ERβ,r=0.379,P=0.005);26.42%of lung adenocarcinomas express GPER1 and ERa,22.64%of lung adenocarcinomas express GPER1 and ERβ,and 30.19%of lung adenocarcinomas express ERa and ERβ.6.GPER1,ERα and ERβ were all positively expressed in lung adenocarcinoma PC-9 cells.7.Estradiol E2 and GPER1 agonist G1 promoted the proliferation of lung adenocarcinoma PC-9 cells through GPER1,and the GPER1 inhibitor G15 inhibited the proliferation of PC-9 cells induced by E2 and G1,which is statistically significant(P<0.05).Conclusions:1.GPER1,ERa and ERβ are all positively expressed in lung adenocarcinoma cells and tissues,suggesting that they may be involved in estrogen-mediated biological effects.2.GPER1 and ERa are associated with clinical stage and lymph node metastasis in patients with lung adenocarcinoma,and the expression of GPER1 and ERa in patients with advanced lung cancer and lymph node metastasis,suggesting that GPER1 and ERa may play an important role in the progression of lung adenocarcinoma.3.There was a positive correlation among GPER1,ERa and ERβ,suggesting that GPER1,ERa and ERβ may play a synergistic role in lung cancer.4.GPER1 can promote the proliferation of lung adenocarcinoma PC-9 cells,suggesting that blocking GPER1 signaling can be considered as a new therapeutic target for lung cancer.