Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma

J Exp Clin Cancer Res. 2015 Sep 4;34(1):95. doi: 10.1186/s13046-015-0212-z.

Abstract

Background: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).

Methods: Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).

Results: p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.

Conclusion: Activation of AKT1 was associated with poor prognosis in ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • ErbB Receptors / metabolism
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / mortality
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Squamous Cell / enzymology*
  • Neoplasms, Squamous Cell / mortality
  • Phosphorylation
  • Prognosis
  • Proportional Hazards Models
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / metabolism*
  • STAT3 Transcription Factor / metabolism

Substances

  • Biomarkers, Tumor
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases