Expression Of BCL3 In Epithelial Ovarian Cancer And Its Clinical Significance

Background and purpose:Epithelial ovarian cancer is occult and lacks effective early detection methods.Most patients find it to be advanced,with a high mortality rate,and the 5-year survival rate has not been improved for nearly 20 years.To further clarify the possible mechanism of the development of epithelial ovarian cancer from a new perspective,and to explore new prognostic molecular markers of epithelial ovarian cancer,which is of great significance for early intervention and reduction of mortality.B-Cell CLL/Lymphoma 3(BCL3),originally found in B-cell chronic lymphocytic leukemia,is considered to be a proto-oncogene,and more and more subsequent studies have shown that BCL3 also plays an important role in a variety of solid tumors,but there is little research on the role of BCL3 in epithelial ovarian cancer at home and abroad.The purpose of this study was to investigate the expression level of BCL3 in epithelial ovarian cancer tissues,the frequency of gene alterations,the frequency of copy number alterations(CNA)and their clinical significance,and to explore the biological processes and regulatory signaling pathways that BCL3 may participate in.Methods:(1)The Oncomine database and GEPIA website were used to analysis of BCL3 mRNA expression in epithelial ovarian cancer tissues.(2)KM plotter database was used to analyze the effect of BCL3 mRNA expression on the prognosis of patients;(3)c Bio Portal website was used to investigate the frequency of BCL3 gene alterations,CNA,and the impact on prognosis.genes that are highly co-expressed with BCL3 were found out;(4)Gene ontology(GO)and Kyoto gene and genome encyclopedia(KEGG)pathway enrichment analysis of BCL3 and its co-expressed genes were performed by Web Gestal website;(5)80 cases of epithelial ovarian cancer and 18 cases of normal ovarian tissue were selected,and the expression level of BCL3 protein in epithelial ovarian cancer was verified by immunohistochemical staining,and the effect of BCL3 nuclear protein expression level on the prognosis of patients was investigated.Results:(1)Five of the seven data sets screened in the Oncomine database showed high expression of BCL3 mRNA in epithelial ovarian cancer(all P values<0.05).The integration analysis of the seven data sets also showed high expression of BCL3 mRNA(P=0.016),GEPIA analysis also confirmed high BCL3 mRNA expression(P <0.05);(2)KM plotter database analysis showed that the overall survival rate(OS)of patients with high BCL3 mRNA expression decreased(P = 0.012);(3)c Bio Portal analysis showed that the frequency of BCL3 gene alteration was 8% and CNA frequency was 3%,which significantly reduced the OS of patients(P values were 0.0161 and 6.206 × 10-6,respectively);(4)GO and KEGG analysis showed that the biological processes involved in BCL3 and its co-expressed genes are mainly: biological regulation,metabolic processes,and cell proliferation,regeneration,and growth,etc.,which were significantly enriched in in TNF,NF-kB,and IL-17 pathways,etc.(5)Immunohistochemical staining confirmed that BCL3 protein was significantly overexpressed in epithelial ovarian cancer(P<0.001).The expression level of nuclear protein was correlated with the presence or absence of local lymph node metastasis(P=0.048),ascites content(P=0.035),and differentiation level(P=0.017).Survival analysis showed that high expression of BCL3 nuclear protein had a tendency to reduce the survival rate of patients,but the difference was not statistically significant(P=0.394).Conclusion:(1)BCL3 mRNA and protein are highly expressed in epithelial ovarian cancer;(2)High expression of BCL3 mRNA reduces OS in patients,and high expression of BCL3 nuclear protein has a tendency to reduce survival rate;(3)Genetic alterations or CNA in BCL3 can reduce OS in patients;(4)BCL3 plays an important role in the occurrence and development of epithelial ovarian cancer,and it can be used as a new molecular marker for prognosis.The research results may provide an important basis for further in-depth mechanism research and exploration of molecular targeted therapy.