Serum CXCL9 levels are associated with tumor progression and treatment outcome in patients with nasopharyngeal carcinoma

PLoS One. 2013 Nov 21;8(11):e80052. doi: 10.1371/journal.pone.0080052. eCollection 2013.

Abstract

Objectives: The aim of this cohort study was to examine the role of the chemokine (C-X-C motif) ligand 9 (CXCL9) on nasopharyngeal carcinoma (NPC).

Materials & methods: Sera from 205 NPC patients and 231 healthy individuals, and 86 NPC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay.

Results: CXCL9 expression was significantly higher in tumors than in normal epithelium. CXCL9 serum concentrations were also significantly higher in NPC patients compared to those in healthy individuals (516.8±617.6 vs. 170.7±375.0 pg/mL, P<0.0001). Serum CXCL9 levels were significantly higher in NPC patients with higher tumor stages, nodal stages, and overall stages (P<0.001, P = 0.001, and P<0.001, respectively). We found a statistically significant correlation between the concentrations of CXCL9 and EBV DNA load in the NPC patients (Spearman's correlation analysis; r = 0.473, P<0.001; 95% confidence interval, 0.346-0.582). Moreover, NPC patients with higher CXCL9 levels (>290 pg/mL, median) before treatment had worse prognoses for overall survival and disease-free survival (P = 0.045 and P = 0.008, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for disease-free survival (P = 0.015).

Conclusion: Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of NPC tumors and the serum level of this ligand may be useful as a prognostic indicator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Chemokine CXCL9 / blood*
  • DNA, Viral / blood
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / blood*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy
  • Real-Time Polymerase Chain Reaction
  • Treatment Outcome
  • Viral Load

Substances

  • CXCL9 protein, human
  • Chemokine CXCL9
  • DNA, Viral

Grants and funding

This study was supported by the grant (NSC99-2314-B-182A-051-MY3) from the National Science Council, the grant (DOH99-TD-C-111-006) from the Department of Health, and by grants (CMRPG32090, CMRPG360213, CMRPG381113, CMRPG390643) from Chang Gung University and Chang Gung Memorial Hospital, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.