The Role Of ITSN1 In Prognosis Prediction Of Breast Cancer And Its Molecular Network Analysis

Objective Intersectin(ITSN)is a highly conserved multi-domain cell adaptor protein,which is mainly involved in biological processes such as endocytosis,exocytosis,and actin cytoskeletal rearrangement.In addition,several studies have found that ITSN1 is also closely related to the occurrence of a variety of diseases.At present,most studies on ITSN1 and tumors center around central nervous system malignancies.ITSN1 is involved in the regulation of proliferation,migration and invasion of malignant tumors.There are few studies on the role of ITSN1 protein in peripheral system malignancies.Breast cancer is a heterogeneous peripheral system malignancy that seriously threatens women's physical and mental health.Therefore,exploring the molecular targets associated with breast cancer prognosis will have great significance for its treatment.Based on the current research status,this study used the Kaplan-Meier Plotter database to analyze the relationship between ITSN1 m RNA expression and prognosis of breast cancer patients,and used multiple databases to analyze the expression level of ITSN1 in various tumors such as breast cancer.Signal pathway and biological process enrichment analysis of genes associated with ITSN1.This study will provide a theoretical basis for further study of the role of ITSN1 in breast cancer,and provide new ideas and directions for the treatment of breast cancer.Methods The Kaplan-Meier Plotter database was used to analyze the relationship between ITSN1 m RNA expression level and prognosis of breast cancer patients with different subtypes and clinicopathological characteristics.The expression of ITSN1,HER2 and ESR1 in breast cancer and other tumors was analyzed by GEPIA database and CCLE database.The GEPIA database was used to analyze the expression of ITSN1,HER2 and ESR1 in breast cancer and normal breast tissues.The EMBL-EBI database was used to analyze the expression of ITSN1,HER2 and ESR1 in different types of breast cancer,breast cancer clinical samples and different breast cancer cell lines.Finally, the Linked Omics database was used to analyze genes related to ITSN1,and these genes were subjected to signal pathway and biological process enrichment analysis.Results 1.The total population of breast cancer with high expression of ITSN1 m RNA has a better prognosis.High expression of ITSN1 m RNA in different types of breast cancer predicts luminal A,luminal B,HER2 negative,histological grade ? and lymph node-positive breast cancer patients with longer recurrence-free survival,lymph node-negative breast cancer patients with high expression of ITSN1 m RNA Have a better overall survival.2.In breast cancer patients with poor cell differentiation(histological grade 2 and histology grade 3),the expression level of ITSN1 m RNA cannot predict the prognosis of patients.3.Patients with HER2-amplified breast cancer or ER-positive breast cancer with low expression of ITSN1 m RNA have better overall survival.Patients with HER2-positive breast cancer or ER-negative breast cancer with low ITSN1 m RNA expression have longer recurrence-free survival.4.The expression of ITSN1 m RNA had no significant effect on the prognosis of breast cancer patients with different progesterone status.5.Further analysis revealed that ITSN1 expression was decreased in breast cancer,and ER and HER2 expression was elevated in breast cancer.6.ITSN1 has the highest expression in Luminal breast cancer,followed by triple negative breast cancer,and the lowest expression in HER2-positive breast cancer.7.ITSN1 expression is lower in most primary breast cancers than in normal breast tissue,with lower expression levels in breast cancer samples and lower expression levels in different breast cancer cell lines.HER2 and ESR1 are expressed at higher levels in most primary breast cancer,breast cancer samples,and breast cancer cell lines.8.A total of 9733 genes were associated with ITSN1,and the expressions of ITSN1 and HER2,ITSN1 and ESR1 were correlated.9.Genes positively associated with ITSN1 in the PI3K-Akt signaling pathway,relaxin signaling pathway,PPAR signaling pathway,actin cytoskeletal rearrangement,cell adhesion,cell migration,cell movement and cell localization,calcium ion binding,Cytoskeletal protein binding,cell adhesion molecule binding,signal receptor binding,focal adhesion,cell-substrate junction,etc.are enriched.10.Genes that are negatively correlated with ITSN1 in mismatch repair,gene duplication,nucleotide excision repair,pyrimidine metabolism,RNA degradation,cell cycle,drug metabolism,purine metabolism,nucleic acid transport,RNA processing,RNA splicing,m RNA processing,RNA binding,drug binding,nucleotide binding,chromosomal regions,nucleoli,nuclear membrane,cell membrane and other aspects are enriched.Conclusion 1.The total population of breast cancer with high expression of ITSN1 m RNA has a better prognosis,but the prognosis of HER2 amplified/positive breast cancer patients and ER positive breast cancer patients with low ITSN1 m RNA expression is better than that of high expression group.2.The expression of ITSN1 in breast cancer is lower than that in normal breast tissue,and the expression of HER2 and ESR1 in breast cancer is higher than that in normal breast tissue.3.Genes associated with ITSN1 are involved in the regulation of PI3K-Akt signaling pathway,actin cytoskeletal rearrangement,cell movement,mismatch repair,gene replication,nucleic acid metabolism,RNA processing,etc.These processes are closely related to tumorigenesis.