Rellationship Between GPER Expression And Clinic Pathological Parameters And Prognosis In Breast Cancer

ObjectiveTo explore the difference between GPER mRNA expression levels in breast cancer tissues and normal breast tissues and its relationship with clinicopathological parameters of breast cancer and to futher analyze the expression of GPER gene in breast cancer and its relationship with prognosis,we use public database big data mining technology to mine and collect breast cancer data sets in the cancer gene atlas(TCGA)containing G-protein coupled estrogen receptor(GPER)mRNA expression.Based on that,combined with clinical breast cancer case data,we selected triple negative breast cancer(TNBC)among the four clinical types of breast cancer for empirical analysis to explore the expression of GPER in triple negative breast cancer and its clinical significance lays the foundation for further exploring whether GPER can be used as an exploratory index for TNBC condition assessment and prognosis judgment.Methods1.The relationship between GPER and clinicopathological parameters and gene co-expression of breast cancer were analyzed according to the operation manual of cbioportal website.2.Kaplan-Meier Plotter database analyzes the effect of GPER expression on recurrence-free survival of breast cancer patients3.Statistical analysis was performed by SPSS21.0 software,and Kruskal-Wallis H test was used to compare the expression difference of GPER mRNA in breast cancer patients with different T stage,N stage,and molecular classification.Pairwise comparison was performed using dunn bonferroni test.Kaplan-Meier method was used to draw survival curve and use Log-rank test to compare the relapse-free survival rate of high and low expression patients.P <0.050 means the difference is statistically significant.4.We collected the data of TNBC patients admitted in our hospital in2013.All breast cancer patients studied had shoowed the negative expression of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(HER-2).The median age of TNBC patients enrolled in the study is 50 years old.The study was approved by the ethics committee,and all TNBC patients participating in the study had a perfect understanding of this study and signed the consent form.5.Inclusion criteria: All patients with breast cancer received modified radical mastectomy.All patients had complete clinical data,including general conditions,pathological diagnosis,tumor staging,treatment,and survival status;no distant metastases before adjuvant chemotherapy.There was no neoadjuvant chemotherapy before surgery.Estrogen,progesterone receptor and HER-2 expression were all negative.All patients had relatively complete follow-up data including time,location and / or time of first recurrence and metastasis and no history of malignant tumors elsewhere.Post-surgery Paraffin or sections of tumor tissue and its adjacent tissues can be obtained by reviewing the pathological section records and reports.The lesions can be clearly measured and the patient’s histological grade,TNM stage,clinical stage,and lymph node metastasis can be confirmed.All patients have completed relevant auxiliary examinations before surgery,and confirmed that they have no liver and kidney abnormalities and no obvious cardiovascular,cerebrovascular,neurological,blood,urinary system diseases.The patients volunteered to participate in this survey and signed a consent form,and the ethics of hospital Committee approval.6.Exclusion criteria:(1)The patients has obvious obstacles in communication;(2)Exclude cases that have received neoadjuvant therapy,chemotherapy,radiotherapy,endocrine therapy,molecular targeted therapy,and breast tumor resection biopsy;(3)Exclude cases that refuse to accept modified radical mastectomy;(4)Exclude cases with multiple tumors or unclear primary lesions;(5)Exclude cases with severe underlying diseases or distant metastases;(6)Exclude women during pregnancy or lactation;(7)Exclude cases that pathological sections,pathological reports or medical history data were incomplete;(8)Exclude cases that refuse to undergo systematic standard treatment or refuse follow-up after operation;(9)Exclude cases of inflammatory breast cancer.Results1.Use the GEPIA database to perform data based on the TCGA dataset.The results showed that compared with breast cancer tissues,GPER expression was higher in normal breast tissues,and the difference was statistically significant(P <0.01).2.Analysis of the TCGA dataset using the c Bio Portal website found that genes related to GPER co-expression were SCN1 B,CST3,PALM,GPR146,MMP28,HSPA12 B,USP6NL,COX4I2,SRPK1,CLDN5,UCHL5,GMPS,HIGD1 B,CLEC3B,PHGR1,USHBP1.3.A total of 3,951 breast cancer patients with GPER expression were collected from the Kaplan-Meier Plotter database.Log-rank test analysis showed that the recurrence-free survival rate of patients with low GPER expression was significantly lower than that of patients with high expression(HR=0.67,95%CI=0.59-0.75,P<0.001=.4.Analysis of the clinicopathological parameters of breast cancer revealed that the expressions of GPER mRNA showed no significant difference in breast cancer patients with different T stage and N stage(H =3.343、6.084;P=0.488、0.193).The expression levels of GPER mRNA in basal-like,HER-2,and luminal breast cancer tissue samples were-0.2393(-0.2507,-0.12611),-0.2639(-0.2759,-0.257),-0.1883(-0.2397,-0.1019),and the difference was statistically significant(H = 106.187,P <0.001).Comparison between two groups revealed that there was a significant difference in GPER mRNA expression between HER-2 and basal-like(P =0.019),HER-2 and luminal,and basal-like and luminal(P<0.001).5.The clinical empirical study of TNBC patients found that the chi-square test P value of GPER(+)and GPER(-)and each clinical parameter were greater than 0.05,indicating that there was no statistically significant difference between GPER expression and each clinical pathological feature.6.Kaplan-meier analysis of GPER protein expression and DFS and OS survival analysis showed that there was no statistically significant difference in DFS and OS between the two groups with different GPER states in TNBC(P > 0.05).Conclusion1.The expression of GPER mRNA in breast cancer is lower than that in normal breast tissue,and the prognosis of patients with low GPER expression is worse,suggesting that GPER is expected to be an independent factor for judging the prognosis of breast cancer patients.However,the impact of GPER expression on breast cancer with different pathological types still needs to be further studied.2.The GPER expression in TNBC patients was not significantly correlated with age,menopause,tumor tissue size,lymph node metastasis,TMN classification,pathological classification,and recurrence.In univariate analysis,there was no significant correlation between GPER positive and TNBC’s 5-year DFS and OS.Multivariate analysis showed that GPER is not an independent prognostic factor.Thus,whether GPER can be used as an exploratory evaluation of TNBC status and prognostic judgment still need to be studied in a larger sample.