Expression Of ACTG2 And MYH11 In Breast Cancer And Their Prognostic Significance

Breast cancer is one of the common malignant tumors in women,and the incidence rate is the first in women's malignant tumors,which seriously endangers women's physical and mental health.Although the combined application of surgical treatment,radiotherapy and chemotherapy has achieved a certain effect in the treatment of breast cancer patients,recurrence and metastasis are still the main causes of death of breast cancer patients.Therefore,studying molecular markers related to breast cancer recurrence and metastasis and seeking new targets that can achieve precise targeted therapy of breast cancer are of great significance in improving the prognosis of patients.Actin gamma 2(ACTG2)and myosin heavy chain 11(MYH11)proteins are abnormally expressed in colorectal cancer,bladder cancer,prostate cancer and other tumors,and may be closely related to the prognosis and metastasis of breast cancer.ObjectiveTo analyze the expression of ACTG2 and MYH11 in breast cancer tissues and to explore the relationship between the expression of ACTG2 and MYH11 and the clinicopathological factors and prognosis of breast cancer.Methods1.Gene chip information from GEO database was obtained to screen differentially expressed genes of breast cancer.2.At the level of mRNA,bioinformatics methods such as Oncomine and GEPIA database were used to explore and analyze the expression of differential genes ACTG2 and MYH11 in breast cancer and their correlation.3.Surgical specimens were collected from 150 patients with invasive ductal carcinoma of the breast diagnosed in the department of pathology,The First Affiliated Hospital of Zhengzhou University from January 1,2012 to December 31,2013.The expression of ACTG2 and MYH11 in breast cancer tissues was detected by immunohistochemistry,and the relationship between ACTG2 and MYH11 expression and clinicopathological factors was analyzed,as well as the correlation between them.4.The Kaplan-Meier method was used to univariately analyze the relationship between ACTG2 and MYH11 expression and overall survival(OS)and disease free survival(DFS)in 150 breast cancer patients,and draw survival curves;Multivariate COX regression analysis was performed to predict the risk factors affecting the prognosis of breast cancer.5.STRING,Coexpedia,Funrich and other analysis software were used to predict the possible mechanism of action of ACTG2,MYH11 and other related genes in breast cancer.Results1.Thirty differentially expressed genes including ACTG2 and MYH11 were screened from the three breast cancer data sets of GSE5764,GSE10797 and GSE45827.2.Oncomine database and GEPIA database predicted that,at the mRNA level,ACTG2 and MYH11 were differentially expressed in breast cancer,colon cancer,bladder cancer,prostate cancer and other tumors,among which ACTG2 and MYH11 were all lower in breast cancer tissues than in normal tissues,and they were positively correlated(r=0.560,P<0.05).3.Immunohistochemical tests showed that ACTG2 protein was located in the cytoplasm,with some cell membranes slightly stained,and the positive staining site of MYH11 protein was the nucleus.In the 150 cases of breast cancer,130(86.7%)had low expression of ACTG2 protein and 128(85.3%)had low expression of MYH11 protein.The expression levels of ACTG2 and MYH11 proteins were positively correlated(r=0.319,P<0.05).4.Clinicopathologic analysis showed that the expression of ACTG2 and MYH11 was significantly associated with lymph node metastasis(P<0.05),but was not associated with age of onset,tumor diameter,histological grade and expression of ER,PR,and HER-2,all of which were P>0.05.In addition,decreased ACTG2 expression was associated with tumor recurrence(P<0.05)5.Univariate survival analysis showed that the median DFS of the group with low ACTG2 protein expression was 62.6 months(95%CI:60.70-64.10).The median DFS of the high expression group was 69.5 months(95%CI:62.60-73.08),and the DFS of the low expression group was significantly lower than that of the high expression group(P<0.05).However,there was no significant correlation between MYH11 expression level and patient survival(P>0.05).6.Multivariate COX regression analysis showed that lymph node metastasis and low MYH11 expression were independent prognostic factors affecting DFS(P>0.05).7.Enrichment analysis of the ACTG2 related interaction genes and co-expressed genes revealed that the regulatory mechanism of ACTG2,MYH11 and other genes in breast cancer may be related to the signaling pathways such as smooth muscle contraction,muscle contraction,and epithelial-mesenchymal transation.ConclusionAt both mRNA and protein levels,ACTG2 and MYH11 were down-regulated in breast cancer tissues.Low expression of ACTG2 and MYH11 is associated with poor prognosis such as lymph node metastasis and tumor recurrence,and both may play a role in tumor invasion and metastasis.ACTG2 and MYH11 are expected to be new prognostic indicators for breast cancer.