Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

Int J Oncol. 2011 Mar;38(3):655-63. doi: 10.3892/ijo.2011.906. Epub 2011 Jan 14.

Abstract

Cancer-associated fibroblasts (CAFs) in the stroma play an important role in influencing the proliferation, invasion and metastasis of cancer cells. Fibroblast activation protein-α (FAP-α) is known as a marker of CAFs, while stromal cell-derived factor-1 (SDF-1) is primarily expressed by CAFs. Herein, we investigated whether the expression levels of these genes are associated with clinical outcome after pre-operative chemoradiotherapy (CRT) in rectal cancer patients. We obtained total RNA from residual cancer stroma using microdissection from a total of 52 rectal cancer specimens from patients who underwent pre-operative CRT, we performed transcriptional analyses, and the serum protein concentrations in 40 matched microdissected specimens were measured by enzyme-linked immunosorbent assay. Additionally, we sought to clarify the location of FAP-α and SDF-1 expression using immunohistochemical staining. Of the 52 patients, 15.6 and 36.8% showed detectable FAP-α and SDF-1 mRNA expression, respectively. A significant correlation was observed between stromal FAP-α and SDF-1 mRNA levels. Moreover, there was a significant correlation between stromal SDF-1 gene expression levels and serum protein levels. Patients who developed distant recurrences after CRT had positive expression of both genes (P<0.05). The positive expression of both genes was also associated with poor probability of recurrence-free and overall survival (P<0.05). Patients with elevated serum SDF-1 levels had equally poor overall survival as those with positive stromal SDF-1 gene expression (P<0.05). In immunohistochemistry, both FAP-α and SDF-1 expression was observed in certain activated fibroblasts. In conclusion, FAP-α and SDF-1 expression was shown to be involved in tumor re-growth and recurrence in rectal cancer patients treated with pre-operative CRT.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Carcinoma / diagnosis*
  • Carcinoma / drug therapy
  • Carcinoma / pathology*
  • Carcinoma / radiotherapy
  • Chemokine CXCL12 / analysis
  • Chemokine CXCL12 / genetics
  • Combined Modality Therapy
  • Female
  • Fibroblasts / pathology*
  • Fibroblasts / physiology
  • Gelatinases / analysis
  • Gelatinases / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matched-Pair Analysis
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Rectal Neoplasms / diagnosis*
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / radiotherapy
  • Serine Endopeptidases / analysis
  • Serine Endopeptidases / genetics

Substances

  • Biomarkers, Tumor
  • Chemokine CXCL12
  • Membrane Proteins
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases