High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients

Br J Cancer. 2013 Sep 3;109(5):1100-8. doi: 10.1038/bjc.2013.440. Epub 2013 Aug 6.

Abstract

Background: Chemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma.

Methods: One hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations.

Results: High CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 -3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P<0.0001). CrkL and c-ABL mRNA expressions were influenced by EGFR mutations. A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma.

Conclusion: We propose that CCR7 and CCL19 are clinically good prognostic factors and that CCR7 is strongly related to CrkL and c-ABL kinase mRNA expression in lung adenocarcinoma.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / surgery
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Chemokine CCL19 / biosynthesis*
  • Chemokine CCL19 / genetics
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-abl / genetics
  • RNA, Messenger / biosynthesis
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CCL19 protein, human
  • CRKL protein
  • Chemokine CCL19
  • Nuclear Proteins
  • RNA, Messenger
  • Receptors, CCR7
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-abl