The prognostic significance of bromodomain PHD-finger transcription factor in colorectal carcinoma and association with vimentin and E-cadherin

J Cancer Res Clin Oncol. 2015 Aug;141(8):1465-74. doi: 10.1007/s00432-015-1937-y. Epub 2015 Feb 26.

Abstract

Purpose: Bromodomain PHD-finger transcription factor (BPTF) is a chromatin-mediated regulation of transcription factor, playing an important role in embryogenesis and differentiation. Epithelial-mesenchymal transition (EMT) has a pivotal role in colorectal cancer (CRC) progression, sharing the similar characteristic with BPTF. Therefore, the aim of this study was to examine the expression and clinical value of BPTF and the correlation with EMT markers in patients with CRC.

Methods: Real-time PCR and Western blot were performed to evaluate the mRNA and protein expression levels of BPTF in 20 pairs of fresh-frozen CRC and non-tumor adjacent tissues (NATs). The expressions of BPTF, vimentin and E-cadherin were examined by immunohistochemical staining in 105 cases of paraffin-embedded primary CRC specimens. In addition, the clinicopathological significance and the prognostic value of BPTF, vimentin and E-cadherin expression were further determined. Then, the correlation of BPTF with vimentin and E-cadherin was also explored.

Results: BPTF mRNA and protein expression were significantly overexpressed in CRC tissues when compared with paired NATs (P < 0.01). The expression levels of BPTF and vimentin in CRC paraffin-embedded specimens were significantly higher than the expression in NATs (P < 0.01), while the expressions of E-cadherin in tumors were obviously lower than in NATs (P < 0.01). Tumors with high expression of BPTF and vimentin, as well as low expression of E-cadherin, were significantly correlated with various adverse clinicopathological factors (P < 0.05). The CRC patients with a high BPTF or vimentin expression had shorter overall survival than those with lower expression (P < 0.05). Furthermore, univariate analysis and multivariate analysis showed that high BPTF expression was an independent prognostic factor for patients with CRC. The last and more interesting Spearman rank correlation analysis and microscopic observation found that the expression of BPTF obviously correlated with the expression of EMT markers vimentin and E-cadherin.

Conclusion: Our results strongly suggested that the high BPTF expression was significantly correlated with tumor progression and may be a potent prognostic marker of CRC. Moreover, BPTF expression was significantly associated with EMT markers vimentin and E-cadherin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Prognosis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vimentin / genetics
  • Vimentin / metabolism*
  • Young Adult

Substances

  • Antigens, Nuclear
  • Biomarkers, Tumor
  • Cadherins
  • Nerve Tissue Proteins
  • Transcription Factors
  • Vimentin
  • fetal Alzheimer antigen