TGFBI Expression in Cancer Stromal Cells is Associated with Poor Prognosis and Hematogenous Recurrence in Esophageal Squamous Cell Carcinoma

Ann Surg Oncol. 2016 Jan;23(1):282-9. doi: 10.1245/s10434-014-4259-4. Epub 2014 Dec 2.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. To improve prognoses in patients with ESCC, we evaluated the potential of transforming growth factor-beta-induced protein (TGFBI), which is overexpressed in ESCC, as a therapeutic candidate.

Methods: We examined the clinical significance of TBFBI in 102 ESCC samples using real-time RT-PCR. Immunohistochemical studies were conducted to examine the localization of TGFBI. Knockdown of TGFBI in cocultured fibroblasts was performed to determine the roles of TGFBI in migration and invasion.

Results: The level of TGFBI in ESCC tissues was higher than that in normal tissues. The high TGFBI expression group (n = 16) had higher TGFB1 expression and more frequent hematogenous recurrence than the low-expression group (n = 86). High TGFBI expression was an independent prognostic factor in patients with ESCC. TGFBI was mainly localized in stromal cells of ESCC. Moreover, suppression of TGFBI in fibroblasts inhibited the migration and invasion capacity of TE8 ESCC cells.

Conclusions: High TGFBI expression in ESCC tissues could be a powerful biomarker of poor prognosis and hematogenous recurrence. TGFBI in stromal cells might be a promising molecular target for ESCC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Cell Movement
  • Cell Proliferation
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Extracellular Matrix Proteins / antagonists & inhibitors
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / metabolism
  • Hematologic Neoplasms / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Survival Rate
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Tumor Cells, Cultured
  • Wound Healing

Substances

  • Biomarkers, Tumor
  • Extracellular Matrix Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Transforming Growth Factor beta
  • betaIG-H3 protein