Clinical Significance Of Low Expression Of CADM3 In Breast Cancer And Preliminary Exploration Of Related Mechanisms

Objective: This study aims to investigate the expression of Cell adhesion molecule 3(CADM3)in breast cancer(BC),its relationship with clinicopathological features,proliferation and migration of breast cancer,and its correlation with MAPK pathway,so as to provide new ideas and evidence for early clinical diagnosis and treatment.Methods: The Cancer Genome Atlas(TCGA)database was used to predict the expression of CADM3 in breast cancer and adjacent normal tissues.Then,clinical and postoperative samples were collected to verify the expression of CADM3 in breast cancer and adjacent normal tissues from the protein and m RNA levels by western blotting(WB)assay and real-time quantitative PCR(q RT-PCR)assay.The relationship between CADM3 and clinicopathologic factors and prognosis of patients was analyzed by using TCGA database bioinformatics analysis and immunohistochemical staining results.The effect of CADM3 on the proliferation of breast cancer cells was studied by cell clonal formation assay and CCK8 assay.The effects of CADM3 on breast cancer cell migration were studied by cell scratch assay and Transwell assay.The TCGA database was used for single gene difference analysis of CADM3 to find its related differential proteins,and the protein interaction network was made.Gene MANIA was used to predict the function of related genes.The GO and KEGG pathways were analyzed by GSEA enrichment analysis to explore the potential biological functions and related action pathways of CADM3.The correlation between CADM3 and MAPK pathway was further explored by WB experiment.Results: 1.The expression level of CADM3 in breast cancer were significantly lower than those in adjacent normal tissues.High expression of CADM3 is associated with better prognosis of breast cancer patients.CADM3 expression is an independent prognostic factor for breast cancer.The expression status of CADM3 was significantly correlated with the expression status of ER and PR,age and molecular typing of breast cancer patients,with higher expression in ER and PR positive patients,age ≤60 and Luminal A breast cancer patients.2.Overexpression of CADM3 in MCF-7 and MDAMB-231 cells can significantly reduce cell proliferation,and overexpression of CADM3 in MDA-MB-231 cells can significantly reduce cell migration.3.Function prediction of CADM3-related genes and GSEA enrichment analysis results suggested that CADM3 was related to MAPK pathway.WB results showed that the phosphorylation of ERK1/2 and JNK1,key proteins of MAPK pathway,was inhibited in MCF-7 and MD-MB-231 cells with high CADM3 expression.Conclusion: 1.CADM3 is low expression in breast cancer,and is associated with good prognosis in breast cancer patients,and can be used as an independent prognostic factor in breast cancer patients.CADM3 expression is higher in patients with ER,PR positive,age ≤60 years,and Luminal A type breast cancer.2.High expression of CADM3 in breast cancer cells can inhibit the proliferation and migration of tumor cells.3.In breast cancer,CADM3 expression is associated with MAPK pathway,and high expression of CADM3 can inhibit protein phosphorylation of ERK1/2 and JNK1.