Overexpression of HSP47 in esophageal squamous cell carcinoma: clinical implications and functional analysis

Dis Esophagus. 2016 Oct;29(7):848-855. doi: 10.1111/dote.12359. Epub 2015 May 8.

Abstract

Several biomarkers of esophageal squamous cell carcinoma (ESCC) have been explored to improve the prognosis of this disease. One of these, the 47-kDa heat shock protein (HSP47), has been screened as a potential biomarker by genomic profiling and is known to be overexpressed in some malignant diseases. In this study, we explored the role and evaluated the prognostic value of HSP47 expression in ESCC. The function of this protein was analyzed by assaying proliferation, wound healing, and colony formation in an HSP47-knockdown ESCC line. The prognostic implication of HSP47 expression was analyzed by immunohistochemical staining in 157 surgical specimens. HSP47 expression level and other clinical variables were analyzed using multivariate Cox proportional hazards models. Silencing of the HSP47 gene in the ESCC cell line inhibited cell proliferation and colony formation. HSP47 was highly expressed in ESCC tissue samples, compared with normal esophageal tissues. The level of immunohistochemical staining of HSP47 and pathologic stage were significantly correlated with overall and recurrence-free survival, as shown by multivariate analysis (P = 0.014 and 0.044, respectively). We found that overexpression of HSP47 is associated with poor prognosis in patients with ESCC and that this is consistent with the function of HSP47 in terms of increased cell proliferation and colony formation. These results suggest that HSP47 is a potential prognostic biomarker for ESCC and merits further research for novel diagnostic and therapeutic applications.

Keywords: esophageal squamous cell carcinoma; heat shock protein 47; prognostic factor.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Esophagus / metabolism
  • Esophagus / pathology
  • Female
  • Gene Knockdown Techniques
  • Gene Silencing / physiology
  • HSP47 Heat-Shock Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Staging
  • Neoplastic Stem Cells / metabolism
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers, Tumor
  • HSP47 Heat-Shock Proteins
  • SERPINH1 protein, human