Clinical significance of preoperative serum concentrations of interleukin-6 as a prognostic marker in patients with esophageal cancer

Esophagus. 2020 Jul;17(3):279-288. doi: 10.1007/s10388-019-00708-6. Epub 2019 Dec 16.

Abstract

Background: Although the clinical outcome of esophageal cancer has recently improved, the relapse rate remains high for all disease stages. At present, there is no diagnostic method to predict the long-term outcome for esophageal cancer. In this study, we evaluated serum preoperative proinflammatory cytokine levels and investigated the correlation between preoperative interleukin-6 (IL-6) and IL-8 levels and survival of patients with esophageal cancer.

Methods: Between 2008 and 2015, we evaluated preoperative serum cytokine levels in 122 patients who underwent esophagectomy for esophageal cancer. Serum IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assays. We investigated the relationship between serum cytokine levels and the response to chemotherapy and survival.

Results: The preoperative IL-6 levels were significantly associated with shorter recurrence-free survival (RFS, p = 0.001) and overall survival (OS, p = 0.001) after esophagectomy. Higher IL-8 levels were significantly associated with RFS (p = 0.018). In the multivariate analysis, age, preoperative chemotherapy, lymph node metastasis, serum C-reactive protein (CRP) levels and serum IL-6 levels (hazard ratio (HR), 2.888; p = 0.049) were significantly independent prognostic factors of RFS. Additionally, age, pathological stage, and serum IL-6 levels (HR, 3.247; p = 0.027) were shown to be significantly independent prognostic factors of OS. Serum IL-6 levels were significantly higher in the non-responder group (pathological response pGrade0 and pGrade1) after neoadjuvant therapy.

Conclusions: High preoperative serum IL-6 levels are associated with a poor response to chemotherapy or chemoradiotherapy and poor prognosis after esophagectomy. Preoperative serum IL-6 levels may be a useful independent prognostic marker for esophageal cancer patients.

Keywords: Esophageal cancer; Esophagectomy; Interleukin-6.

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • C-Reactive Protein / analysis
  • Chemoradiotherapy / methods
  • Chemoradiotherapy / statistics & numerical data
  • Drug Therapy / methods
  • Drug Therapy / statistics & numerical data
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery*
  • Esophagectomy / methods*
  • Esophagectomy / statistics & numerical data
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Interleukin-8 / blood
  • Japan / epidemiology
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoadjuvant Therapy / statistics & numerical data
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Staging / adverse effects
  • Outcome Assessment, Health Care
  • Preoperative Care / standards
  • Prognosis
  • Retrospective Studies
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Interleukin-6
  • Interleukin-8
  • C-Reactive Protein