Abstract
Simple SummaryFew studies have examined the impact of primary tumor location on clinical outcome in patients with early-stage nodal diffuse large B-cell lymphoma (DLBCL). The objective of this study was to identify the association between primary tumor location and early-stage nodal DLBCL patient prognosis using a large population-based cohort and make an effort to uncover its underlying molecular mechanism using a public database. Our result shows that the prognosis of early-stage nodal DLBCL patients with tumors growing under the diaphragm is poorer. After screening DEGs and carrying out enrichment analysis, we found early-stage nodal diffuse large B-cell lymphoma located in different sites having different genetic characteristics. These results emphasize the importance of the primary tumor site on clinical decision-making and prognosis of patients with early-stage nodal diffuse large B-cell lymphoma.The prognostic role of primary tumor location for clinical outcomes of patients with early-stage nodal diffuse large B-cell lymphoma (DLBCL) remains uncertain. We evaluated the relationship between primary tumor site and overall survival (OS) in 9738 early-stage nodal DLBCL patients from the Surveillance, Epidemiology, and End Results (SEER) database. The primary site of the tumors was characterized as supradiaphragm and subdiaphragm according to the definition of lymph node distribution in the Ann Arbor staging. The OS was significantly better for patients of the supradiaphragm group (n = 6038) compared to the ones from the subdiaphragm group (n = 3655) (hazard ratio (HR) 1.24; 95%CI: 1.16–1.33; P < 0.001), and it was preserved after propensity score matching (PSM) (HR 1.15; 95% CI: 1.07–1.24; P < 0.001). Gene enrichment analyses demonstrated that the subdiaphragm group has an upregulated extracellular matrix (ECM)-related signaling, which reportedly can promote growth, invasion, and metastasis of the cancer, and downregulated interferon response, which is considered to have anti-tumor function. Our results indicate the two tumor locations (supradiaphragm and subdiaphragm) presented different prognostic implications for the overall survival, suggesting that the tumor’s location could serve as a prognostic biomarker for early-stage nodal DLBCL patients.
Highlights
The diffuse large B-cell lymphoma (DLBCL) is the most common subtype of nonHodgkin’s lymphoma (NHL), accounting for approximately 25 percent of NHL cases [1].It is highly heterogeneous in terms of clinical presentation, morphology, genetics, and biologic behavior
The focus of this study is to explore a feasible and simple grouping method for patients with early-stage nodal DLBCL based on the SEER database, that is, patients with nodal DLBCL in different primary sites are divided into the subdiaphragm group (Sub-DLBCL) and supradiaphragm group (Sup-DLBCL) according to the definition of lymph node distribution in Ann Arbor staging
We aim to explore the overall survival of patients with early-stage nodal DLBCL located on both sides of the diaphragm during the rituximab era, and try to identify the potential molecular mechanism between them, in an attempt to assist clinicians to better predict the prognosis of DLBCL patients with different parts and to provide a basis for clinical decision-making
Summary
The diffuse large B-cell lymphoma (DLBCL) is the most common subtype of nonHodgkin’s lymphoma (NHL), accounting for approximately 25 percent of NHL cases [1]. It is highly heterogeneous in terms of clinical presentation, morphology, genetics, and biologic behavior. Despite the fact that early-stage DLBCL patients generally present favorable prognosis, about 30% of them is expected to relapse [7]. It is vital to explore the factors that can predict recurrence and chemotherapy resistance, and to identify the factors that can affect the prognosis of earlystage nodal DLBCL patients, aiming to contribute to disease progression prediction and support clinical decisions
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