Differential expression of NF-κB heterodimer RelA/p50 in human urothelial carcinoma

Background. Urothelial carcinoma (UC) is the fifth most common malignancy that accounts for 5% of all cancers. Diagnostic markers that predict UC progressions are inadequate. NF-kappa B contributes towards disease progression upon constitutive activation in many solid tumors. The nuclear localization of NF-kappa B indicates increased transcriptional activity while cytoplasmic localization indicates the inactive protein repository that can be utilized readily by a malignant cell. This study delineates the nuclear and cytoplasmic differential expression of NF-kappa B heterodimers in UC progression. Methods. The involvement of the NF-kappa B proteins in UC was analyzed in silico using cytoscape. The expression of NF-kappa B heterodimers was analyzed by immunohistochemistry. Results. PINA4MS app in cytoscape revealed over expression of RelA and suppression of NF-kappa BI (p50 precursor) in UC whereas the expression of NF-kappa B target proteins remained unhindered. Immunohistochemical localization showed nuclear RelA/p50 in low grade UC whereas in high grade only RelA expression was observed. Conversely, cytoplasmic expression of RelA/p50 remained extensive across high and low grade UC tissues (p < 0.005). RelA nuclear and cytoplasmic expression (p < 0.005) was directly proportional to the disease progression. In our study, some of the high-grade UC tissues with squamous differentiation and muscle invasion had extensive nuclear p50 localization. The phenomenon of RelA/p50 expression seen increased in low-grade UC than high grade UC might be due to their interaction with other members of NF-kappa B family of proteins. Thus, NF-kappa B RelA/p50 differential expression may play a unique role in UC pathogenesis and can serve as a biomarker for diagnosis.