1.The Function And Mechanism Of IGJ In Breast Cancer 2.Immunoglobulin Superfamily Member 10 Is A Novel Prognostic Biomarker For Breast Cancer

CHAPTER I:THE FUNCTION AND MECHANISM OF IGJ IN BREAST CANCERBackground: Metastasis is the primary cause of death in breast cancer patients.Exploring the mechanism of breast cancer metastasis is particularly important to improve the prognosis of breast cancer patients.This study aims to explore the role and mechanism of IGJ in breast cancer.Methods:We analyzed the high-throughput RNA-sequencing data from The Cancer Genome Atlas project(TCGA)to explore potential metastasis-related genes in breast cancer.Quantitative polymerase chain reaction(q-PCR)and western blot were used to detect the expression of IGJ in breast cancer tissues and cell lines.We carried out immunohistochemical(IHC)to confirm IGJ expression in paired breast cancer tissues.We explored the biologic functions of IGJ in breast cancer cells by CCK-8,trans-well assay,wound healing and in vivo assays.We also used q-PCR,western blot,immunofluorescence(IF)and bioinformatic analysis to explore the potential mechanisms and pathways associated with IGJ in breast cancer.Results:We found the expression of IGJ was significantly higher in adjacent normal breast tissues than that in breast cancer tissues.Immunohistochemical(IHC)staining revealed that the protein expression of IGJ was lower in metastatic breast cancer tissues when compared with that in adjacent normal breast tissues and non-metastatic breast cancer tissues.The multivariate Cox regression analysis demonstrated that IGJwas an independent prognostic factor in breast cancer for OS(HR=0.59,95% CI: 0.421-0.866,p=0.007)and RFS(HR=0.651,95% CI: 0.461-0.837,p=0.001).Overexpress of IGJ inhibits proliferation,migration,invasion and EMT in breast cancer cells.IGJ inhibits the activation of NF-κB signaling pathway in breast cancer.Moreover,IGJ may inhibit the invasion and metastasis of breast cancer by suppressing the NF-κB signaling pathwayConclusion: In conclusion,we found IGJ was downregulated in breast cancer.IGJ also provide a prognostic value for breast cancer patients.Importantly,IGJ may inhibit metastasis of breast cancer by suppressing the activation of NF-κB signaling pathway.Our research may provide a new therapeutic target for the treatment of metastatic breast cancer.CHAPTER II:IMMUNOGLOBULIN SUPERFAMILY MEMBER 10 IS A NOVEL PROGNOSTIC BIOMARKER FOR BREAST CANCERBackground: Immunoglobulin superfamily member 10(IGSF10)is a member of the immunoglobulin superfamily that is expressed at high levels in both the gallbladder and ovary.Currently,the role and possible mechanism of IGSF10 in breast cancer remain unclear.Methods: By applying quantitative polymerase chain reaction(q-PCR)and immunohistochemistry(IHC),the expression of IGSF10 in breast cancer cells and tissues was detected.We collected the clinical information from 700 patients with breast cancer in The Cancer Genome Atlas(TCGA),and analyzed the relationship between IGSF10 expression and the clinicopathological features and survival outcomes of these patients.The potential mechanisms and pathways associated with IGSF10 in breast cancer were explored by performing a gene set enrichment analysis(GSEA).Results:According to TCGA data,q-PCR and IHC experiments,levels of the IGSF10 m RNA and protein were significantly decreased in breast cancer tissues.IGSF10 expressionwas significantly correlated with age,tumor size,and tumor stage.Moreover,shorter overall survival(OS)and relapse-free survival(RFS)correlated with lower IGSF10 expression,according to the survival analysis.The multivariate analysis identified that IGSF10 as an independent prognostic factor for the OS(hazard ratio(HR)=1.793,95% confidence interval(CI): 1.141–2.815,P=0.011)and RFS(HR=2.298,95% CI: 1.317–4.010,P=0.003)of patients with breast cancer.Based on the GSEA,IGSF10 was involved in DNA repair,cell cycle,and glycolysis.IGSF10 was also associated with the PI3K/Akt/m TOR and m TORC1 signaling pathways.Conclusion: This study revealed a clear relationship between IGSF10 expression and the tumorigenesis of breast cancer for the first time.Therefore,further studies are needed to understand the mechanism of IGSF10 in breast cancer.