CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

Oncol Rep. 2009 Oct;22(4):745-55. doi: 10.3892/or_00000496.


The aim of this study was to examine the expression of CD44v6, CD54, Cdx2, CXCL5, Cyclin B1, MMP-7, nm23, RCAS1 and Survivin in primary gastric cancer and to investigate whether these molecules were useful in predicting the lymph node status. They were selected as candidates for indicators of lymph node metastasis from various kinds of cancer-associated genes reported previously. In 135 cases of radically resected primary gastric adenocarcinoma, we investigated the association between the expression of these molecules and clinocopathologic factors by immunohistochemistry. The results revealed that the expression of CD44v6 and MMP-7 were significantly associated with lymph node status. By contrast, nuclear Cdx2 expression was found to be inversely correlated with lymph node metastasis. Moreover, multivariate analysis demonstrated that CD44v6, MMP-7 and nuclear Cdx2 were independent predictors for lymph node status. In conclusion, our results suggest that positive expression of both CD44v6 and MMP-7, and negative expression of nuclear Cdx2 may serve as powerful predictors of lymph node metastasis in gastric cancer. Combined evaluation of these markers could be further useful to predict lymph node status clinically.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis
  • Biomarkers, Tumor / analysis
  • CDX2 Transcription Factor
  • Cell Nucleus / metabolism
  • Chemokine CXCL5 / biosynthesis
  • Cyclin B / biosynthesis
  • Cyclin B1
  • Female
  • Homeodomain Proteins / biosynthesis*
  • Humans
  • Hyaluronan Receptors / biosynthesis*
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / pathology*
  • Male
  • Matrix Metalloproteinase 7 / biosynthesis*
  • Microtubule-Associated Proteins / biosynthesis
  • Middle Aged
  • NM23 Nucleoside Diphosphate Kinases / biosynthesis
  • Neoplasm Staging
  • Prognosis
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survivin


  • Antigens, Neoplasm
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • CCNB1 protein, human
  • CD44v6 antigen
  • CDX2 Transcription Factor
  • CDX2 protein, human
  • CXCL5 protein, human
  • Chemokine CXCL5
  • Cyclin B
  • Cyclin B1
  • EBAG9 protein, human
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • NM23 Nucleoside Diphosphate Kinases
  • Survivin
  • Intercellular Adhesion Molecule-1
  • NME1 protein, human
  • Matrix Metalloproteinase 7