Correlation between overall survival and differential plasma and tissue tumor marker expression in nasopharyngeal carcinoma patients with different sites of organ metastasis

Oncotarget. 2016 Aug 16;7(33):53217-53229. doi: 10.18632/oncotarget.10676.

Abstract

Differential overall survival of nasopharyngeal carcinoma (NPC) with different organ site metastases has been documented. Here, we attempted to determine the underlying mechanisms by assessing plasma and tumor tissue markers in relation to patient survival. Pretreatment plasma Epstein-Barr virus (EBV) DNA concentrations, cytokines and tissue macrophages, proliferation and apoptosis markers were determined in 178 patients with metastatic NPC. The median overall survival (OS) was 19 months. Patients with single organ metastases had better outcomes than those with multiple organ metastases (median OS: 26 months vs. 16 months), with statistical significance. Among the single organ involvement cases, patients with lung metastasis only showed longer survival than those with bone or liver involvement (median OS: 50 months vs. 21 months vs. 18 months; P < 0.001). Pretreatment plasma EBV DNA concentrations were lower in patients with lung metastasis than bone or liver metastasis among single organ site groups. Plasma interferon-γ-inducible protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1) expression levels were correlated with differential single organ site metastasis OS and EBV DNA load. Liver metastatic tissue had higher density of infiltrating macrophages and proliferative index than the lung metastatic group. Low pretreatment plasma EBV DNA load, expression of cytokines, such as IP-10 and MCP-1, tissue macrophage infiltration, and proliferative index may contribute to the differences in overall survival.

Keywords: EB virus; EBV DNA; IP-10; metastasis; nasopharyngeal carcinoma.

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / genetics
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / genetics
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Herpesvirus 4, Human / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / blood
  • Nasopharyngeal Neoplasms / complications
  • Nasopharyngeal Neoplasms / genetics*
  • Neoplasm Metastasis
  • Organ Specificity / genetics*

Substances

  • Biomarkers, Tumor
  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CXCL10
  • DNA, Viral