Plasma Cytokines Correlated With Disease Characteristics, Progression-Free Survival, and Overall Survival in Testicular Germ-Cell Tumor Patients

Clin Genitourin Cancer. 2017 Jun;15(3):411-416.e2. doi: 10.1016/j.clgc.2017.01.027. Epub 2017 Feb 8.

Abstract

Background: Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients.

Patients and methods: This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays.

Results: At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-β were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria.

Conclusion: We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches.

Keywords: Biomarker; Cytokines; Plasma; Prognosis; Testicular germ cell tumors.

MeSH terms

  • Cytokines / blood*
  • Disease Progression
  • Disease-Free Survival
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / therapeutic use
  • Male
  • Melphalan / administration & dosage
  • Melphalan / therapeutic use
  • Neoplasm Metastasis
  • Neoplasms, Germ Cell and Embryonal / blood
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / immunology
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / therapeutic use
  • Prognosis
  • Prospective Studies
  • Testicular Neoplasms / blood
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / immunology
  • Testicular Neoplasms / mortality
  • Translational Research, Biomedical

Substances

  • Cytokines
  • Immunoglobulin G
  • Organoplatinum Compounds
  • antineoplastic agent K 18
  • Melphalan

Supplementary concepts

  • Testicular Germ Cell Tumor