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

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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.

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References

  • Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA (2009) Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest 119:1438–1449

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Alderton GK (2013) Metastasis: epithelial to mesenchymal and back again. Nat Rev Cancer 13:3

    Article  PubMed  Google Scholar 

  • Bastid J (2012) EMT in carcinoma progression and dissemination: facts, unanswered questions, and clinical considerations. Cancer Metastasis Rev 31:277–283

    Article  PubMed  Google Scholar 

  • Brenner H, Kloor M, Pox CP (2014) Colorectal cancer. Lancet 383:1490-1502

  • Buganim Y, Goldstein I, Lipson D, Milyavsky M, Polak-Charcon S, Mardoukh C, Solomon H, Kalo E, Madar S, Brosh R, Perelman M, Navon R, Goldfinger N, Barshack I, Yakhini Z, Rotter V (2010) A novel translocation breakpoint within the BPTF gene is associated with a pre-malignant phenotype. PLoS One 5:e9657

    Article  PubMed  PubMed Central  Google Scholar 

  • Carvajal-Vergara X, Sevilla A, D’Souza SL, Ang YS, Schaniel C, Lee DF, Yang L, Kaplan AD, Adler ED, Rozov R, Ge Y, Cohen N, Edelmann LJ, Chang B, Waghray A, Su J, Pardo S, Lichtenbelt KD, Tartaglia M, Gelb BD, Lemischka IR (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465:808–812

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Craene BD, Berx G (2012) Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 13:97–110

    Article  Google Scholar 

  • Fan CC, Wang TY, Cheng YA, Jiang SS, Cheng CW, Lee AY, Kao TY (2013) Expression of E-cadherin, Twist, and p53 and their prognostic value in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol 139:1735–1744

    Article  PubMed  CAS  Google Scholar 

  • Goller T, Vauti F, Ramasamy S, Arnold HH (2008) Transcriptional regulator BPTF/FAC1 is essential for trophoblast differentiation during early mouse development. Mol Cell Biol 28:6819–6827

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  PubMed  CAS  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  • Jones MH, Hamana N, Shimane M (2000) Identification and characterization of BPTF, a novel bromodomain transcription factor. Genomics 63:35–39

    Article  PubMed  CAS  Google Scholar 

  • Kalluri R (2009) EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 119:1417–1419

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kim K, Punj V, Choi J, Heo K, Kim JM, Laird PW, An W (2013) Gene dysregulation by histone variant in bladder cancer. Epigenet Chromatin 6:34

    Article  CAS  Google Scholar 

  • Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15:178–196

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, Matta J, Tessarollo L, Zhang YE, Ko MS, Kuehn MR, Yamaguchi TP, Wu C (2008) Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells. PLoS Genet 4:e1000241

    Article  PubMed  PubMed Central  Google Scholar 

  • Lim J, Thiery JP (2012) Epithelial-mesenchymal transitions: insights from development. Development 139:3471–3486

    Article  PubMed  CAS  Google Scholar 

  • Malouf GG, Taube JH, Lu Y, Roysarkar T, Panjarian S, Estecio MR, Jelinek J, Yamazaki J, Raynal NJ, Long H, Tahara T, Tinnirello A, Ramachandran P, Zhang XY, Liang S, Mani SA, Issa JP (2013) Architecture of epigenetic reprogramming following Twist1-mediated epithelial-mesenchymal transition. Genome Biol 14:R144

    Article  PubMed  PubMed Central  Google Scholar 

  • Mulder KW, Wang X, Escriu C, Ito Y, Schwarz RF, Gillis J, Sirokmany G, Donati G, Uribe-Lewis S, Pavlidis P, Murrell A, Markowetz F, Watt FM (2012) Diverse epigenetic strategies interact to control epidermal differentiation. Nat Cell Biol 14:753–763

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Tillo E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M, Darling DS, Dean DC, Castells A, Postigo A (2012) EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci 69:3429–3456

    Article  PubMed  CAS  Google Scholar 

  • Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Wen M, Kwon Y, Xu Y, Liu Y, Zhang P, He X, Wang Q, Huang Y, Jen KY, Labarge MA, You L, Kogan SC, Gray JW, Mao JH, Wei G (2014) CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression. Cancer Res 74(2):520-531

  • Wysocka J, Swigut T, Xiao H, Milne TA, Kwon SY, Landry J, Kauer M, Tackett AJ, Chait BT, Badenhorst P, Wu C, Allis CD (2006) A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature 442:86–90

    PubMed  CAS  Google Scholar 

  • Xiao S, Liu L, Fang M, Zhou X, Peng X, Long J, Lu X (2014) BPTF associated with EMT indicates negative prognosis in patients with hepatocellular carcinoma. Dig Dis Sci. doi:10.1007/s10620-014-3411-0

  • Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14:818–829

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Chen Huang for many helpful discussions and technical support. We also thank Dr. F. Zheng and Drs. J. Liu for polishing the English writing of this manuscript.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of General Surgery, Affiliated Nanhua Hospital of University of South China, 336 South Dongfeng Road, Hengyang, 421002, Hunan Province, China

    Shuai Xiao, Longfei Liu, Xianzhou Lu, Jianwu Long, Xiaojun Zhou & Min Fang

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  1. Shuai Xiao
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  2. Longfei Liu
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  3. Xianzhou Lu
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  4. Jianwu Long
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  5. Xiaojun Zhou
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Corresponding author

Correspondence to Shuai Xiao.

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432_2015_1937_MOESM1_ESM.jpg

Fig. S1 Postoperative 5-year survival curves of patients with CRC or HCC. (A)The CRC patients with high BPTF expression had shorter overall survival than those with low BPTF expression (P=0.002) (n = 105). (B)The HCC patients with high BPTF expression had shorter overall survival than those with low BPTF expression (P=0.001) (n = 106). Supplementary material 1 (JPEG 80 kb)

Supplementary material 2 (DOC 33 kb)

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Xiao, S., Liu, L., Lu, X. et al. The prognostic significance of bromodomain PHD-finger transcription factor in colorectal carcinoma and association with vimentin and E-cadherin. J Cancer Res Clin Oncol 141, 1465–1474 (2015). https://doi.org/10.1007/s00432-015-1937-y

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  • DOI: https://doi.org/10.1007/s00432-015-1937-y

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