Abstract
Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma in the world, is highly heterogeneous. Although current therapies have improved the clinical outcome, 30–40% of the patients are still not cured. Thus, novel treatment options such as targeted therapy is urgently needed. Accumulating evidence suggests that 14-3-3beta protein plays an important role in tumorigenesis and tumor progression. However, the specific roles of 14-3-3beta in DLBCL are still poorly understood. In this study, we retrospectively analyzed 120 archived wax blocks obtained from patients with DLBCL (n = 70) and non-neoplastic lymph nodes (n = 50). Immunohistochemical staining showed that 14-3-3beta gene expression was significantly decreased in DLBCL tissues (P < 0.001) compared to that in non-neoplastic lymph nodes. Low 14-3-3beta expression was significantly correlated with extra-nodal status (P = 0.026), serum LDH level (P = 0.023) and adverse survival of DLBCL patients. In survival analyses, low 14-3-3beta expression was significantly associated with adverse overall survival of the DLBCL patients (P = 0.003). Using the Kaplan-Meier analysis module of the R2 microarray analysis and visualization platform (http://r2.amc.nl), we also confirmed that low expression of 14-3-3beta gene had inferior overall survival in DLBCL patients. Based on our results, we conclude that low expression of 14-3-3beta is associated with adverse survival of diffuse large B-cell lymphoma patients, suggesting a novel prognostic marker and potential therapeutic target.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of adult non-Hodgkin’s lymphoma, and its incidence has been increasing in recent years, accounting for ∼30% of all cases of non-Hodgkin’s lymphoma in Western countries [1] and up to 45.8% in China [2]
We used immunohistochemistry to compare the expression of 14-3-3beta in tissue samples from DLBCL patients and reactive hyperplasia of lymph nodes from control subjects
Immunohistochemistry (IHC) showed that positive 14-3-3beta expression occurred mostly in the cytoplasm, with weaker expression in the nucleus in the DLBCL group, whereas this pattern was reversed in the non-neoplastic lymph nodes (Figure 1)
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of adult non-Hodgkin’s lymphoma, and its incidence has been increasing in recent years, accounting for ∼30% of all cases of non-Hodgkin’s lymphoma in Western countries [1] and up to 45.8% in China [2]. DLBCL shows high heterogeneity in terms of clinical manifestations, genetic findings, treatment response, and prognosis. Expression of 14-3-3beta in DLBCL in early recurrence. Chien et al [9] reported that 14-3-3beta expression was significantly upregulated in untreated gastric cancer cells. Overall, these studies support the possibility of YWHAB acting as an oncogene. We explored the potential association of 14-3-3beta protein expression in DLBCL with clinical outcomes. These findings may provide new insight into the pathogenic mechanisms of DLBCL and suggest novel treatment strategies
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