The Correlation Between HMGCR Expression And Breast Cancer:A Study Based On Public Databases

BackgroundNowadays,the incidence rate of breast cancer is the highest in women.The survival rate of breast cancer patients is significantly improved due to the diversity of progressive treatment methods.However,because of the unknown etiology and treatment target of breast cancer,some patients will still have recurrence and metastasis.Therefore,exploring new therapeutic targets and developing new targeted drugs have become the focus of breast cancer treatment.In recent years,the characteristics of tumor metabolism have attracted great attention of researchers.Mevalonate pathway(MVP)is a highly conserved metabolic pathway.The loss and accumulation of upstream and downstream products are closely related to the proliferation,metastasis,differentiation and apoptosis of tumor cells.3-hydroxy-3-methylglutaryl coenzyme-A reductase(HMGCR)is one of the start rate limiting enzymes of MVP.The activity of HMGCR plays an important role in the regulation of MVP products.Therefore,to explore the relationship between the expression of HMGCR and breast cancer may provide a new target for the treatment of breast cancer patients.PurposeThe purpose of this study is to explore the relationship between the expression of HMGCR mRNA and protein and the clinicopathological characteristics and prognosis of breast cancer patients by using public databases and clinical samples of immunohistochemistry analysis,so as to provide a new target for the treatment decision-making and prognosis prediction of breast cancer patients.Methods1.The expression of HMGCR mRNA in breast cancer and normal breast tissues:TCGA database was used to obtain the expression of HMGCR mRNA in breast cancer and normal breast tissues,and the box plot of the expression of HMGCR gene was drawn to determine whether it was a differential gene.2.The relationship between HMGCR mRNA expression and clinicopathological characteristics of breast cancer patients:(1)The expression data of HMGCR mRNA in breast cancer patients with different clinicopathological characteristics were included in GEO databases,and the relationship between HMGCR mRNA expression and clinicopathological characteristics was analyzed.(2)Logistic analysis:Significant clinicopathological features of univariate analysis in the database were included in logistic analysis to evaluate independent risk factors related to HMGCR mRNA expression.3.The relationship between the expression level of HMGCR mRNA and the survival of breast cancer patients:(1)According to the median value of HMGCR mRNA expression,the breast cancer patients and their subgroups were divided into high expression group and low expression group,and the survival curves were drawn respectively to clarify the effect of HMGCR mRNA expression on the survival of breast cancer patients.(2)Cox multivariate analysis:The significant variables of single factor survival analysis were included in Cox proportional risk model for multiple factor analysis to further explore the independent risk factors that affect the survival of breast cancer patients.4.The expression of HMGCR protein in breast cancer and normal breast tissue:the expression of HMGCR protein in breast cancer and normal breast tissue was analyzed by immunohistochemistry in 209 breast cancer patients diagnosed by biopsy from June 2012 to June 2014 in our hospital.5.The relationship between HMGCR protein expression and clinicopathological characteristics of breast cancer patients:(1)The relationship between the expression of HMGCR protein and different clinicopathological characteristics was analyzed by immunohistochemistry in 209 cases of breast cancer in our hospital.(2)Logistic analysis:the significant clinicopathological features of single factor analysis of immunohistochemistry were included in logistic analysis to evaluate the independent risk factors related to HMGCR protein expression.6.The relationship between the expression of HMGCR protein and the survival of breast cancer patients:(1)according to the results of immunohistochemistry,the expression of HMGCR protein in breast cancer patients in our hospital was divided into high expression group and low expression group,and the survival curve was drawn to clarify the effect of HMGCR protein expression on the survival of breast cancer patients.(2)Cox multivariate analysis:The significant variables of single factor survival analysis were included in Cox proportional risk model for multiple factor analysis to further explore the independent risk factors that affect the survival of breast cancer patients.Results1.Compared with normal breast tissue,the expression of HMGCR mRNA in breast cancer tissue increased significantly(P<0.05).2.Tumor diameter(OR=1.141,OR(95%CI):1.069-1.164),axillary lymph node metastasis(OR=1.299,OR(95%CI):1.029-1.672)are independent risk factors for high HMGCR mRNA expression.3.The high expression of HMGCR mRNA and the decrease of Disease-free Survival were positively correlated with tumor diameter(P<0.001,HR=1.627,95%Cl=1.263-1.991)and axillary lymph node metastasis(P=0.033,HR=1.363,95%Cl=1.167-1.559).4.Compared with normal breast tissue,the expression of HMGCR protein in breast cancer tissue increased significantly(P<0.05)5.Tumor diameter(OR=1.419,OR(95%CI):1.051-1.799)is an independent risk factor for high HMGCR protein expression.6.The high expression of HMGCR protein and the decrease of Disease-free Survival were positively correlated with tumor diameter(P<0.001,HR=1.793,95%C1=1.360-2.226).Conclusion1.The expression of HMGCR in breast cancer is higher than that in normal breast tissue.2.Positive correlation between tumor diameter and HMGCR expression.3.The high expression of HMGCR in breast cancer patients is a potential predictor of poor prognosis.