The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients

Background: The Glasgow Prognostic Score (GPS) measures inflammation and proves its prognostic value in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL) which is commonly combined with inflammatory lesion. Given inflammatory chemokines play an important role in tumor progression, we hypothesized that chemokines might influence ENKTL aggressiveness through interaction with their receptors in the tumor tissue. Methods: We measured the serum levels of C-X-C motif ligand 13 (CXCL13) in 69 patients with ENKTL who received non-anthracycline-based chemotherapy and/or concurrent chemoradiotherapy because CXCL13 is thought to have a pro-tumor effect through interaction with its receptor, the C-X-C chemokine receptor 5 (CXCR5). We analyzed the association of serum CXCL13 with the GPS, and their prognostic relevance. The levels of CXCL13 were measured using a multiplex chemokine assay on archived frozen serum samples. Results: Patients were categorized into high and low CXCL13 groups if they had CXCL13 levels above or below the median value of 29.1 pg/mL, respectively. The high CXCL13 group and grouping by the GPS showed a significant association with poor progression-free survival. The elevated serum levels of CXCL13 were also significantly associated with a high score of the GPS. High CXCL13 levels and GPS were significantly associated with high tumor burden predicting poor prognosis including stages III/IV, extranasal presentation, bone marrow invasion, and presence of Epstein-Barr virus (EBV) DNA in blood. Furthermore, serum CXCL13 and GPS discriminated patients at risk of treatment failure among patients with low tumor burden (stage I/II) and non-detectable EBV DNA. Conclusions: Serum levels of CXCL13 were associated with the prognostic value of GPS. Grouping by the serum CXCL13 might predict survival outcomes in patients with ENKTL, suggesting that it is a potential therapeutic target.