IL-6, IL-8 and TNF-α levels correlate with disease stage in breast cancer patients

Adv Clin Exp Med. 2017 May-Jun;26(3):421-426. doi: 10.17219/acem/62120.

Abstract

Background: Breast cancer is the most common cancer in Chinese women. Inflammation contributes to tumor progression and can be induced by excessive production of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). However, how their levels relate to the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) by the tumor has not been investigated.

Objectives: The aim of the study is to more fully understand the significance of serum IL-6, IL-8 and TNF-α in breast cancers with different ER, PR and HER2 status.

Material and methods: Preoperative serum samples were collected from 110 patients diagnosed with ductal carcinoma and 30 healthy control subjects. IL-6, IL-8 and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA). Associations of cytokine levels with clinical tumor stage were evaluated, and correlations of serum cytokine levels with ER, PR and HER2 expression were determined using the Pearson correlation coefficient.

Results: Serum levels of IL-6 and IL-8 were significantly higher in the subjects with ductal carcinoma than in the controls, and strongly correlated with clinical tumor stage, lymph node metastasis, and ER and HER2 antigen expression (p < 0.05). TNF-α levels in stage III carcinoma patients were significantly higher than in the controls (p < 0.01) and were associated with lymph node metastasis (p < 0.01). A strong positive correlation was found between IL-8 and TNF-α levels in the cancer patients (p < 0.0001).

Conclusions: The study showed that IL-6, IL-8 and TNF-α levels correlated with clinical disease stage and lymph node metastasis as well as with ER and HER2 antigen expression. Specifically, IL-6 and IL-8 seem to have significant potential as prognostic cancer biomarkers. Analyzing serum cytokine levels might help identify patients with a poor prognosis who may benefit from more aggressive disease management.

Keywords: TNF-α; biomarkers; breast cancer; interleukin-6; interleukin-8.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / blood*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Interleukin-8 / blood*
  • Lymphatic Metastasis / pathology
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • Biomarkers, Tumor
  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Necrosis Factor-alpha
  • ERBB2 protein, human
  • Receptor, ErbB-2