TITLE:
Diagnostic and Prognostic Value of Nuclear Factor Kappa-B in Diffuse Large B Cell Lymphoma in Egyptian Patients with Hepatitis C Virus Genotype 4
AUTHORS:
Nabil El Halawani, Manal El Sordi, Mona Aiad, Bassma El Sabaa, Alia Hashim
KEYWORDS:
Diffuse Large B-Cell Lymphoma, NF-κB, Hepatitis C Virus, Germinal Center-B, Activated B-Cell-Like, Antiviral Therapy
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.9 No.3,
July
31,
2019
ABSTRACT: Background: Members of the NFκB [p65] family have potential diagnostic and prognostic role in various inflammatory diseases and Lymphomas. Aim: We studied NFκB [p65] in paraffin blocks of hepatitis-C-virus [HCV] positive genotype-4 and HCV negative diffuse large B-cell lymphoma [DLBCL] patients, aiming at identification of its differential expression and prognosis in DLBCL and its subtypes; GCB and ABC. This is to establish its relation to HCV infection and its role in lymphogenesis. Besides assessing the role of new directly acting antiviral drugs [Sofusbuvir/Ledipasvir] concomitantly administered to [CHOP] combination in HCV positive DLBCL. Subjects and Methods: NFκB [p65] expression was assessed using Anti-NFκB [p65] antibody semi-quantitative technique in 30 newly diagnosed DLBCL patients [HCV positive [n = 15], HCV negative [n = 15]. Results: NFκB [p65] expression was higher in the HCV positive DLBCL patients than their HCV negative counterpart, with a positive correlation with the viral load [r = 0.536, p = 0.088]. NFκB [p65] expression was significantly more frequently detected in the ABC subtype than GCB subtype [p = 0.04]. Patients who expressed NFκB [p65] had higher incidence of extranodal involvement, advanced stages, higher LDH levels and IPI score. Besides, the expression of NFκB [P65] revealed an inferior overall response [OR] [p = 0.044]. Higher complete response rates to CHOP concomitantly with antiviral [ledipasvir/sofosbuvir] were encountered in the HCV positive group. In HCV positive group, NFκB [P65] displayed a positive relationship with the viral load and liver enzymes [p = 0.04], besides an inverse relation with serum albumin. This raises the possibility that NFκB [p65] expression is suggestive of the hepatic necro-inflammation in HCV patients. The ABC group presented more in advanced stages than GCB. Higher frequency of the ABC subgroup exhibited intermediate to high viral load, while it was less in the GCB. A statistically significant difference was found in the NFκB [p65] positive patients as regards MUM1 expression among the two groups [p ≤ 0.001]. Double positive [CD10+, MUM1+] and triple negative [CD10-, BCL6-, MUM1-] cases were encountered in the HCV positive group, and were characterized with a high NFκB [p65] expression. Conclusion: NFκB [p65] is expressed in patients with DLBCL, more frequently in ABC than in GCB subtypes. Expression of NFκB [p65] is associated with poor response to therapy in DLBCL. The NFκB [p65] disclosed an increased expression in HCV positive DLBCL compared to HCV negative group. The viral load displayed a positive correlation with the NFκB [p65] expression. Simultaneous administration of DAAs in combination with CHOP disclosed a better response and high tolerability.