The Expression Of CCBL2 Used As A Biomarker To Evaluate The Prognosis Of Breast Cancer Patients

ObjectiveCysteine conjugate beta-lyase 2(CCBL2),also known as kynurenine aminotransferase 3(KAT3)or glutamine transaminase L(GTL),plays an essential role in transamination and cytochrome P450.Breast cancer(BC)is currently the most common cancer in female,and some biomarkers of breast cancer have been used in clinical practice,but the current biomarkers still have their limitations.In this paper,grade 3 expression data of The Cancer Genome Atlas-Breast Carcinoma(TCGA-BRCA)were analyzed to investigate the expression level of CCBL2 in breast cancer tissues and its relationship with survival and prognosis of breast cancer patients.The expression of CCBL2 in breast cancer cell lines was preliminarily verified by experiments.MethodsThe mRNA and protein expression of CCBL2 in BC cell lines and patient samples were detected by RT-q PCR and immunohistochemistry(IHC).The expression data of CCBL2 in various breast cancer cell lines were downloaded from the Cancer Cell Line Encyclopedia(CCLE)database.BC patients’ clinical information and RNA-Seq expression were acquired via The Cancer Genome Atlas(TCGA)database.Patients were categorized into high/low CCBL2 expression groups based on the optimal cutoff value(8.973)determined by receiver operating characteristic(ROC)curve.We investigated CCBL2 and clinicopathological characteristics’ relationship using Chi-square tests,estimated diagnostic capacity using ROC curves and drew survival curves using Kaplan–Meier estimate.We compared survival differences using Cox regression and externally validated using Gene Expression Omnibus(GEO)database.We evaluated enriched signaling pathways using gene set enrichment analysis(GSEA),explored CCBL2 and relevant genes’ relationship using tumor immunoassay resource(TIMER)databases and used the human protein atlas(HPA)for pan-cancer analysis and IHC.ResultsCCBL2 was overexpressed in normal human cell lines and tissues.CCBL2 expression was lower in BC tissues(n=1104)than in normal tissues(n=114),validated by GEO database.Several clinicopathologic features were related to CCBL2,especially estrogen receptor(ER),progesterone receptor(PR)and clinical stages.The low expression group exhibited poor survival.CCBL2’s area under curve(AUC)analysis showed finite diagnostic capacity.Multivariate cox-regression analysis indicated CCBL2 independently predicted BC survival.GSEA showed enriched pathways:early estrogen response,MYC and so on.CCBL2 positively correlated with estrogen,progesterone and androgen receptors.CCBL2 was downregulated in most cancers and was associated with their survival,including renal and ovarian cancers.ConclusionThe expression of CCBL2 was lower in tumor tissues than in healthy breast tissues.Low CCBL2 expression is a promising poor breast cancer survival independent prognostic marker.