Chemokine profiling in serum from patients with ovarian cancer reveals candidate biomarkers for recurrence and immune infiltration

Oncol Rep. 2019 Feb;41(2):1238-1252. doi: 10.3892/or.2018.6886. Epub 2018 Nov 27.

Abstract

The management of advanced ovarian cancer is challenging due to the high frequency of recurrence, often associated with the development of resistance to platinum‑based chemotherapy. Molecular analyses revealed the complexity of ovarian cancer with particular emphasis on the immune system, which may contribute to disease progression and response to treatment. Cytokines and chemokines mediate the cross‑talk between cancer and immune cells, and therefore, present as potential biomarkers, reflecting the tumor microenvironment. A panel of circulating C‑C motif chemokine ligand (CCL) and C‑X‑C motif chemokine ligand (CXCL) chemokines were examined in the serum of 40 high‑grade patients with ovarian cancer prior to primary surgery. The level of immune infiltration in tumors was also analyzed. The preoperative levels of chemokines differ between patients. Elevated levels of circulating CXCL4 + CCL20 + CXCL1 combination can discriminate patients with shorter recurrence‑free survival and overall survival. The presence of tumor‑infiltrating T lymphocytes was detected in half of the patients. The mRNA expression analysis suggests the presence of antitumoral and immunosuppressive elements in the tumor microenvironment. The combination of circulating CXCL9 + CXCL10 can distinguish immune‑infiltrated tumors that will lead to shorter recurrence‑free survival. The results suggest that preoperative profiling of circulating chemokines in patients with ovarian cancer may provide valuable information regarding tumor recurrence and immune infiltration. The findings demonstrate that combinations have better prognostic utility than single chemokines, and may serve as patient stratification tools.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Chemokine CCL20 / blood*
  • Chemokine CXCL1 / blood*
  • Chemokine CXCL9 / blood*
  • Disease Progression
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / immunology
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / immunology*
  • T-Lymphocytes / immunology
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor
  • CCL20 protein, human
  • CXCL1 protein, human
  • CXCL9 protein, human
  • Chemokine CCL20
  • Chemokine CXCL1
  • Chemokine CXCL9