Prognostication of Primary Tumor Location in Early-Stage Nodal Diffuse Large B-Cell Lymphoma: An Analysis of the SEER Database

SIMPLE SUMMARY: Few 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. ABSTRACT: 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.