Decreased Expression of PDHE1α Predicts Worse Clinical Outcome in Esophageal Squamous Cell Carcinoma

Anticancer Res. 2015 Oct;35(10):5533-8.

Abstract

Background: Aerobic glycolysis is an important hallmark of cancer cells. Deficiency of pyruvate dehydrogenase component α subunit (PDHE1α) leads to mitochondrial dysfunction and promotes glycolysis. Therefore, studies on the expression of PDHE1α in cancer are warranted.

Patients and methods: The PDHE1α protein was immunohistochemically investigated and analyzed in 157 samples of surgically dissected esophageal squamous cell carcinoma (ESCC) and 21 'normal' esophageal epithelia tissues.

Results: PDHE1α protein expression was lower in ESCC. Absence of PDHE1α protein expression in tumor cells was found in 77.1% of cases. Negativity for PDHE1α protein in tumor cells was correlated with poor tumor differentiation (p<0.05) and shorter overall survival (p<0.05).

Conclusion: Lack of PDHE1α protein expression in ESCC is associated with poor prognosis. Our findings also verify the existence of aerobic glycolysis switch in ESCC, and strongly advocate novel therapeutic strategies in reversing the Warburg effect in tumors.

Keywords: PDHE1α; Warburg effect; esophageal squamous cell carcinoma; immunohistochemistry; overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Pyruvate Dehydrogenase (Lipoamide) / metabolism*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Pyruvate Dehydrogenase (Lipoamide)
  • pyruvate dehydrogenase E1alpha subunit