Abstract
In this study we investigated whether the expression of cyclin D2 (CCND2) mRNA in activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) was correlated with the efficacy of Rituximab combined with chemotherapy (R-CHOP) treatment and patient prognosis. Tissue microarray and RNAscope in situ hybridization were used to detect CCND2 mRNA expression in 117 ABC-DLBCL tumor tissues and associations between CCND2 expression and progression-free survival was analyzed. We also downloaded data from the Gene Expression Omnibus database to analyze CCND2 expression and the efficacy of R-CHOP treatment and prognosis of patients with newly diagnosed ABC-DLBCL. The positive expression rate of CCND2 mRNA in patients with ABC-DLBCL was 41%. Progression-free survival was significantly lower in patients with positive rather than those negative CCND2 expression (P = 0.005). Further, R-CHOP treatment was significantly more effective for patients with ABC-DLBCL with high CCND2 mRNA expression than those with low expression (P = 0.039). Multivariate regression analysis suggested that high CCND2 expression was an independent prognostic risk factor for progression-free survival for patients with ABC-DLBCL who achieved complete remission after R-CHOP treatment. CCND2 expression in ABC-DLBCL tumors, detected by RNA in situ hybridization, is closely related to the curative effect of R-CHOP and patient prognosis following R-CHOP treatment, and represents a potential biomarker for treatment efficacy and prognostic evaluation in patients with ABC-DLBCL.
Highlights
Non-Hodgkin’s lymphoma (NHL) is a common malignant tumor of lymphoid tissues, responsible for morbidity and mortality, ranking seventh and ninth, respectively, among malignant tumors in western developed countries [1]
Patients newly diagnosed with activated B-cell-like (ABC)-diffuse large B-cell lymphoma (DLBCL) undergo standard RCHOP as the first-line treatment, and follow-up evaluations are performed regularly every 3 months by CT to determine whether recurrence or progression occurred
Analysis of follow-up data demonstrated that patients with ABC-DLBCL negative for Cyclin D2 (CCND2) expression had significantly superior progression-free survival than those positive for CCND2 mRNA (χ 2 = 8.005, P = 0.005; Figure 2)
Summary
Non-Hodgkin’s lymphoma (NHL) is a common malignant tumor of lymphoid tissues, responsible for morbidity and mortality, ranking seventh and ninth, respectively, among malignant tumors in western developed countries [1]. Among NHL subtypes, diffuse large B-cell lymphoma (DLBCL) is the most common, and can be divided into activated B-cell-like (ABC)-DLBCL, germinal center B-cell-like (GCB)-DLBCL and unclassified according to its different cellular origins; ABC-DLBCL is associated with poorer prognosis [3]. The accepted first-line treatment regimen for DLBCL is rituximab combined with chemotherapy (R-CHOP). The R-CHOP regimen can significantly improve the outcome for patients with DLBCL; the overall cure rate is only ∼60%, and long-term progression-free survival of patients with ABC-DLBCL following first-line treatment remains
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