Expression of CXCR4 and VEGF-C is correlated with lymph node metastasis in non-small cell lung cancer

Thorac Cancer. 2017 Nov;8(6):634-641. doi: 10.1111/1759-7714.12500. Epub 2017 Sep 19.

Abstract

Background: This study investigated the correlations between CXCR4 and VEGF-C expression and lymph node metastasis in non-small cell lung cancer (NSCLC).

Methods: Tumor specimens, lymph nodes, and normal lung tissues were obtained from 110 NSCLC patients who underwent complete resection. Quantitative reverse transcription-PCR and immunohistochemistry assays were conducted to evaluate messenger RNA (mRNA) and protein expression of CXCR4 and VEGF-C. Logistic regression analysis was performed to determine the independent risk factors for lymph node metastasis in NSCLC.

Results: CXCR4 and VEGF-C mRNA expression were observed in 78 (70.9%) and 64 (58.2%) lung cancer tissues, while CXCR4 and VEGF-C protein expression were observed in 76 (69.9%) and 58 (52.7%) lung cancer tissues, respectively. The expression rates of CXCR4 and VEGF-C mRNA in metastatic lymph nodes were 84.8% and 66.7%, which were higher than that in non-metastatic lymph nodes (27.3% and 18.2%), respectively. Logistic regression analysis revealed that positive expressions of CXCR4 and VEGF-C mRNA were independent risk factors for lymph node metastasis in NSCLC. Furthermore, combined expression of CXCR4 and VEGF-C showed a much higher odds ratio than CXCR4 or VEGF-C expression alone.

Conclusions: CXCR4 and VEGF-C were highly expressed in lung cancer tissues and metastatic lymph nodes. CXCR4 and VEGF-C expression levels were significantly correlated with lymph node metastasis in NSCLC. CXCR4 and VEGF-C might synergically promote lymphatic metastasis in lung cancer and might be a clinical predictor of lymph node metastasis in NSCLC patients.

Keywords: CXCR4; VEGF-C; lymph node metastasis; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Logistic Models
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism*
  • Vascular Endothelial Growth Factor C / genetics*
  • Vascular Endothelial Growth Factor C / metabolism*

Substances

  • Biomarkers, Tumor
  • CXCR4 protein, human
  • Receptors, CXCR4
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor C