Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer

Dig Dis Sci. 2013 Jun;58(6):1581-9. doi: 10.1007/s10620-012-2552-2. Epub 2013 Jan 12.

Abstract

Background: The first identified lysine-specific demethylase, LSD1, plays an important role in the metastatic progression of several types of cancer.

Aims: The aim of this study was to investigate LSD1, E-cadherin, and N-cadherin expression in colon cancer specimens and their clinical significance.

Methods: The expression of LSD1, E-cadherin, and N-cadherin in colon cancer specimens was determined by immunohistochemistry, and the relationship between the expression of the respective molecules and clinicopathological characteristics was analyzed.

Results: The positive expression rates of LSD1, E-cadherin, and N-cadherin in colon cancer specimens were 66.7 % (72/108), 85.2 % (92/108), and 41.7 % (45/108), respectively. LSD1 was significantly more highly expressed in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P < 0.05). Further analysis demonstrated that LSD1 expression was positively correlated with lymph node and distant metastases (P < 0.05). However, E-cadherin expression was significantly downregulated in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P < 0.05), whereas the expression of N-cadherin did not differ significantly according to clinical and pathological characteristics (P > 0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression (r s = -0.318, P = 0.001), but not evidently correlated with N-cadherin expression (r s = 0.182, P = 0.06). Colon cancer specimens with positive LSD1 expression and negative E-cadherin expression were correlated with significantly lower overall survival.

Conclusions: LSD1 showed a significantly higher expression, in contrast to the significantly lower expression of E-cadherin, in colon cancer specimens classified as high TNM stage lesions and with distant metastasis. Positive expression of LSD1 and negative expression of E-cadherin may be predictors of a worse colon cancer prognosis.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Cadherins / metabolism*
  • Case-Control Studies
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Down-Regulation
  • Female
  • Histone Demethylases / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Up-Regulation

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH2 protein, human
  • Cadherins
  • Histone Demethylases
  • KDM1A protein, human