title: The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients.
abstract: 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.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kstwoh@skku.edu.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, Korea. kstwoh@skku.edu.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea. kjryu@hanmail.net.
authors.forename: Kyung Ju
authors.initials: KJ
authors.lastname: Ryu
authors.affiliation: Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University, Seoul, Korea. hongmineui@gmail.com.
authors.forename: Mineui
authors.initials: M
authors.lastname: Hong
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. yhko310@skku.edu.
authors.forename: Young Hyeh
authors.initials: YH
authors.lastname: Ko
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wskimsmc@skku.edu.
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D054382:Chemokine CXCL13 / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D054391:Lymphoma, Extranodal NK-T-Cell / Q000097:blood* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13