Expression Level And Clinical Significance Of RFC4 In Breast Cancer

Background: Breast cancer(BC)is one of the most common malignant tumors in the world.Among female cancers,the morbidity ranks first and the mortality ranks second,and it shows a trend of increasing year by year.Recurrence and distant metastasis are the major causes of treatment failure and death in breast cancer patients.Therefore,it is very important to explore effective and sensitive biomarkers as therapeutic targets and prognostic indicators.RFC4 is the fourth subunit of human replicator C and plays an important role in DNA synthesis and repair after damage.Studies have shown that RFC4 is abnormally expressed in a variety of malignancies.However,studies on RFC4 and breast cancer have rarely been reported.The expression and clinical significance of RFC4 in breast cancer patients have not been reported.Objective: To detect the expression of RFC4 in breast cancer u sing bioinformatics analysis and immunohistochemistry,to investigat e the relationship between the expression level of RFC4 and clinico pathological parameters and prognosis of breast cancer patients,and to explore whether RFC4 can be used as a therapeutic target for breast cancer and a biomarker for assessing prognosis.Methods:1.In this study,bioinformatics analysis of RFC4 was performed based on several online public databases to explore the p ossibility of RFC4 as a breast cancer biomarker.The expression of RFC4 m RNA in breast cancer was first analyzed by three databases,Oncomine,TIMER2.0 and UALCAN,then the relationship between the expression level of this gene and clinical indicators in breast c ancer patients was analyzed using the bc-Gen Ex Miner database,and finally the Kaplan-Meier plotter database to assess the impact of RFC4 expression on survival and prognosis of breast cancer patient s.2.114 breast cancer tissue specimens from the First Hospital of South China University with perfect clinical data were collected and made into tissue microarrays,and the expression level of RFC4 protein in the tissue microarrays was detected using immunohistochemistry,and the relationship between RFC4 protein expression level and clinicopathological characteristics of breast cancer patients was analyzed by SPSS,and finally,according to the follow-up data,the Kaplan-Meier method was used to plot the overall survival curve(OS)and disease-free survival curve(DFS)based on the follow-up data.Results: 1.Comprehensive bioinformatics analysis of the RFC4 gene revealed that the gene showed different expression levels in a variety of tumors.in breast cancer,RFC4 m RNA expression was s ignificantly higher than in normal breast tissue.High RFC4 expressi on was strongly associated with age ≤51 years,negative estrogen re ceptor(ER)and progesterone receptor(PR),positive human epiderm al growth factor receptor 2(HER-2),lymph node metastasis,basal-ce ll breast cancer,triple negative breast cancer(TNBC),and higher S BR grade(P<0.05).Patients with high expression of RFC4 had wors e overall survival(OS),relapse-free survival(RFS),and distant met astasis-free survival(DMFS).2.Immunohistochemical results showed that RFC4 protein was highly expressed in breast cancer tissues and its expression level was associated with clinical stage and distant metastasis(P<0.05).patients with high RFC4 protein expression had shorter overall survival and disease-free survival.Conclusion: RFC4 is highly expressed in breast cancer,and patients with high expression have poor prognosis.RFC4 is expected to be a potential therapeutic target for breast cancer and a biomarker for prognosis assessment.