Experimental Study Of The Expression Of TK1,GATA3,E2F1 And FOXO1 In Breast Invasive Ductal Carcinoma By Transcriptome Sequencing Combined With Immunohistochemistry

Background: Breast cancer is a malignant tumor that has been seriously threated women's health,a variety of factors together to promote the occurrence and development of breast cancer,in which genes play an important role in breast cancer.In the occurrence and development of breast cancer,activated oncogenes,inactivated tumor suppressor genes and related regulatory factors are the key factors inducing breast cancer,and play an important role in the development of breast cancer.At present,the main clinical methods for the treatment of breast cancer include surgery,radiotherapy and chemotherapy,endocrine and targeted therapy,which prolong the survival time and improve the prognosis of patients with breast cancer,but recurrence and metastasis are the main factors affecting the prognosis of patients,so how to improve the accuracy of diagnosis is an urgent problem to be solved.In this study,four genes closely related to breast cancer were screened,in which the expression of thymidine kinase1(TK1),GATA binding protein 3(GATA3)and E2 F transcription factor 1(E2F1)was increased in breast cancer,the expression of forkhead box transcription factor O1(FOXO1)is down-regulated in breast cancer,which is contrary to the first three genes.Although the expression of TK1,GATA3,E2F1 and FOXO1 in breast cancer has been reported,there is no study about the combined application in breast cancer.This study investigated the value of TK1,GATA3,E2F1 and FOXO1 in the diagnosis of breast cancer by transcriptome sequencing and immunohistochemistry.Objective: 1.To investigate whether there is a difference in the expression of TK1,GATA3,E2F1 and FOXO1 in fresh breast invasive ductal carcinoma tissues and adjacent normal tissues.2.To investigate whether there is a difference in the expression of TK1,GATA3,E2F1 and FOXO1 in paraffin sections of breast invasive ductal carcinoma and benign breast lesions.3.To explore the value of combined detection of TK1,GATA3,E2F1 and FOXO1 in the clinical diagnosis of breast invasive ductal carcinoma.Method: 1.The expression of TK1,GATA3,E2F1 and FOXO1 of 6 pairs of fresh breast invasive ductal carcinoma and adjacent normal tissues was detected by transcriptome sequencing on Illumina HiSeq platform.2.Detect the expression of TK1,GATA3,E2F1 and FOXO1 in paraffin sections of 74 cases of breast invasive ductal carcinoma and 35 cases of benign breast lesions by immunohistochemistry,and analyze the clinical value.Results:1.The results of transcriptome sequencing showed that compared with normal tissues adjacent to the cancer,the expression levels of TK1,GATA3 and E2F1 were increased in breast invasive ductal carcinoma tissues,and the expression level of FOXO1 was decreased in breast invasive ductal carcinoma tissues.2.Immunohistochemical results showed that TK1 and GATA3 were highly expressed in breast invasive ductal carcinoma tissues compared with benign breast lesions,FOXO1 was lowly expressed in breast invasive ductal carcinoma tissues,there was no significant difference in the expression of E2F1 between breast invasive ductal carcinoma tissues and benign breast lesions(P>0.05).3.The expression of FOXO1 in breast invasive ductal carcinoma tissues was correlated with tumor size(P<0.05),but it was not associated with age,ER,PR,HER2,lymph node metastasis and TNM clinical stage(P>0.05).4.The diagnostic sensitivity of TK1 is 70.3%,the specificity is 100%,and the sensitivity and specificity of GATA3 diagnosis are 32.4% and 97.1%,respectively,the sensitivity of FOXO1 for diagnosis of breast invasive ductal carcinoma is 86.5%,the specificity is 80%.After the combination of TK1,GATA3,FOXO1,the sensitivity of the diagnosis was greatly improved,which was 98.6%.Conclusion: The results of transcriptome sequencing were consistent with the results of immunohistochemistry,compared with the control group,the expression of TK1 and GATA3 increases in breast invasive ductal carcinoma,and the expression of FOXO1 decreases,suggesting that TK1,GATA3 and FOXO1 may be involved in the occurrence and development of breast invasive ductal carcinoma.The sensitivity of the combination of TK1,GATA3 and FOXO1 was as high as 98.6%,which was higher than the sensitivity of the marker when used alone,and it may have certain value in the diagnosis of breast invasive ductal carcinoma.