Expression Of C4BPA Gene In Breast Cancer And Its Correlation With Prognosis Of The Patients Based On Bioinformatics Analysis

BackgroundBreast cancer(BC)is one of the most common malignancies with the highest morbidity and mortality in women throughout the world.In spite of recent advances in the diagnosis and therapy of BC,the recurrent and metastatic BC remains incurable,and have become the greatest challenge in clinical treatment.Thus,it is urgent but challenging for researchers to determine the precise mechanism of BC development and discover sensitive biomarkers and innovative therapeutics to improve the clinical diagnosis and treatment of BC,respectively.C4 BPA is the gene encoding the alpha chain of C4 BP protein,which is involved in the complement system.Currently,C4 BPA has been detected in different types of tumours such as pancreatic cancer,lung cancer and ovarian cancers and can be predicted as an effective novel biomarker for early diagnosis and prognosis of tumors,but its role is still blank in breast cancer.ObjectivesThe purpose of this study was to detect the expression and prognosis of the complement component 4 binding protein alpha(C4BPA)in the breast cancer tissue and the corresponding adjacent tissue.MethodsBioinformatics analysis was performed on BC-BRCA data from TCGA database and RNA-Seq data from GTEX(normal sample)downloaded from UCSC XENA database.Firstly,we analyzed the expression level of C4 BPA in BC and normal tissues.Then we screened out the differential genes of the high and low expression groups of C4 BPA,and analyzed Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene set enrichment analysis(GSEA)pathway enrichment analysis,the relationship between the expression of the C4 BPA with the immune infiltration level in BC and Protein–protein interaction(PPI)network analysis.Furthermore,we analyzed the relationship between the expression of the C4 BPA with the clinicopathological characteristics and prognosis of patients.In addition,we developed a multivariate Cox regression model to predict patient prognosis,and it consisted of the expression level of C4 BPA gene and other clinicopathological parameters which were significant in multivariate analysis.A nomogram and calibration curve were depicted to evaluate the prognosis prediction model of C4 BPA.Finally,the prognostic analysis of the various subgroups of BRCA in TCGA breast invasive carcinoma was performed.ResultsIn this study,we performed a comprehensive bioinformatics analysis of C4 BPA.C4BPA was not consistently expressed in breast cancer tissues and normal breast tissues,and was significantly less expressed in breast cancer tissues than in normal breast tissues(P< 0.001).Using ROC curves,C4 BPA could be used as an ideal biomarker to differentiate breast cancer from non-tumour tissue(AUC 0.870,Cl:0.830-0.909).Moreover,C4 BPA expression was associated with T stage,ER status,PAM50,histological type,age and race(p = 0.01,0.003,P<0.001,P< 0.001,P<0.001,P<0.001),but not with N stage,M stage,pathological stage,HER-2 status,anatomic neoplasm subdivisions,TP53 status and PIK3 CA status.In addition,progression-free interval(PFI)and overall survival(OS)were analysed by the Kaplan-Meier method,with patients in the C4 BPA low expression group having significantly shorter PFI and OS than those in the C4 BPA high expression group.COX regression analysis was used to explore the clinicopathological significance of C4 BPA expression.Cox multifactor analysis showed that C4 BPA low expression,M stage,and pathological stage were independent risk factors for PFI in patients with invasive breast cancer(P=0.003,0.012,P < 0.001);and C4 BPA low expression,M stage,pathological stage,and ER status were independent risk factors for independent risk factors for OS(P=0.013,0.002,0.041,0.004).Prognostic analysis of the various subgroups of BRCA in TCGA breast invasive carcinoma showed that patients with C4 BPA low expressing breast carcinoma were more likely to be ER positive(HR=0.45(0.29-0.70),P < 0.001),PR positive(HR=0.46(0.29-0.75),P=0.002),HER2 negative(HR=0.47(0.27-0.83),P=0.009),Luminal A type of PAM50(HR=0.58(0.35-0.95),P=0.032)had shorter progression-free interval;in addition,they had shorter progression-free interval in ER-positive(HR=0.45(0.29-0.69),PR-positive(HR=0.29-0.69),P <0.001)(HR=0.61(0.44-0.86),P=0.005),Luminal A(HR=0.59(0.36-0.97),P=0.038,)Luminal B(HR=0.21(0.05-0.90),P=0.035),and PAM50 subgroups..Conclusions(1)C4BPA is significantly less expressed in breast cancer tissues than in normal breast tissues;(2)C4BPA can be used as an ideal biomarker to distinguish breast cancer from non-tumor tissue;(3)Low expression of C4 BPA may be associated with poor prognosis in breast cancer,and it may be a promising prognostic biomarker in breast cancer;(4)In patients with Luminal A breast cancer,those with low C4 BPA expression may have worse PFI and OS.