Expression Of STAT1 In Breast Cancer,Bioinformatics Analysis And Experimental Study Of Biological Function

Background Breast cancer is the second leading cause of cancer death in the world,and recurrence and metastasis are the main causes of death.Among them,the triple-negative breast cancer(TNBC)subtype has a higher degree of intratumoral heterogeneity and invasion and metastasis^[1],and the mutation rate is about 7-13 times higher than other subtypes of breast cancer^[2];high mutation rate Make TNBC have higher immunogenicity and more tumor immune infiltration.At present,the molecular mechanism driving the pathogenesis of TNBC has not been fully elucidated.Signal transducer and activator of transcription-1(STAT1)respond to cytokines and growth factors in the body to maintain normal immune regulatory functions.It has been found that STAT1 is abnormally activated in a variety of malignant tumors.For example,the expression of STAT1 in breast cancer and bladder cancer is significantly higher than its adjacent normal tissues^[3],but the specific prognostic value is still controversial.Based on the active state of STAT1,this topic explores the biological function of STAT1 in tumors.Objective 1.To analyze the biological function and process of STAT1 in breast cancer through bioinformatics;2.To observe the expression of STAT1 and its active state(p STAT1)in breast cancer tissue specimens;3.In breast cancer cell lines Activate STAT1 to study the changes of its biological function;4.Analyze the correlation between STAT1 and immune checkpoint PD-L1 in breast cancer,and explore the function of STAT1 in tumor immunity.Method 1.The transcriptome data and clinical data of 1222breast cancer patients in the Cancer Genome Atlas(TCGA)database were used for bioinformatics analysis of STAT1.2.Using immunohistochemical technology to detect the expression of STAT1/p STAT1 protein in breast cancer and benign breast lesions.3.Use q RT-PCR,Western Blot and flow cytometry to detect and analyze breast cancer cell lines at the gene,protein and cell level.4.Measure the proliferation and migration ability of cells in the active state of STAT1 by CCK8 and cell damage and scratch migration experiments.Results 1.Bioinformatics analysis showed that STAT1 can regulate immunity,inhibit tumor,inhibit cell growth and promote cell apoptosis,which is related to tumor staging and metastasis in situ of breast cancer.2.STAT1 and p STAT1 are highly expressed in breast cancer,and p STAT1 is more highly expressed in triple-negative breast cancer.3.p STAT1inhibits the proliferation of breast cancer cell lines MCF-7,MDA-MB-468 and promotes migration.4.p STAT1 up-regulates the expression of PD-L1 in breast cancer and induces breast cancer immunosuppression.Conclusion p STAT1 is highly expressed in breast cancer,the cell proliferation is weakened,the migration ability is enhanced,and the expression of PD-L1 is induced.It is speculated that the high expression of p STAT1 in breast cancer can protect tumor cells from immune attack,maintain a low response and high resistance state,retain their migration ability,and thus metastasize under suitable conditions.