SpringerLink
Log in

High level of FOXC1 expression is associated with poor prognosis in pancreatic ductal adenocarcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Accumulating evidence for overexpression of FOXC1 in various types of human cancer suggests that it plays a key role in tumor biology. However, little is known about the function of FOXC1 in pancreatic ductal adenocarcinoma (PDA). This study was to investigate the expression profile of FOXC1 in PDA and its clinical significance. We detected the expression profile of FOXC1 mRNA and protein in PDA tissue and in corresponding normal tissue by quantitative reverse-transcriptase polymerase chain reaction and western blotting. Immunohistochemistry was also used in the detection of FOXC1 protein expression. The clinicopathological implications of these proteins were analyzed statistically. Survival analysis was performed to assess prognostic significance. FOXC1 mRNA was overexpressed in PDA tissue when compared with corresponding normal tissue, so was FOXC1 protein. The overexpression of FOXC1 was significantly associated with the degree of clinical stage (p < 0.001), histological differentiation (p = 0.002), and lymph node metastases (p < 0.001). Survival analysis revealed that overexpression of FOXC1 is associated with a poorer prognosis. These observations suggest that FOXC1 plays a key role in PDA and therefore may provide an opportunity for develo** a novel therapeutic target as well as a prognostic marker in PDA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics. 2007. CA Cancer J Clin. 2007;57:43–66.

    Article  PubMed  Google Scholar 

  2. Lillemoe KD, Yeo CJ, Cameron JL. Pancreatic cancer: state-of-the-art care. CA Cancer J Clin. 2000;50:241–68.

    Article  PubMed  CAS  Google Scholar 

  3. Kleeff J, Friess H. Nonmetastatic pancreatic cancer: many trials, little progress. J Clin Oncol. 2008;26:3100. doi:10.1200/JCO.2008.17.0985. author reply 3100-a-3101.

    Article  PubMed  Google Scholar 

  4. Myatt SS, Lam EW. The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer. 2007;7(11):847–59. doi:10.1038/nrc2223.

    Article  PubMed  CAS  Google Scholar 

  5. Kidson SH, Kume T, Deng K, Winfrey V, Hogan BL. The forkhead/winged-helix gene, Mf1, is necessary for the normal development of the cornea and formation of the anterior chamber in the mouse eye. Dev Biol. 1999;211:306–22.

    Article  PubMed  CAS  Google Scholar 

  6. Kume T, Deng KY, Winfrey V, Gould DB, Walter MA, Hogan BL. The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus. Cell. 1998;93:985–96.

    Article  PubMed  CAS  Google Scholar 

  7. Mears AJ, Jordan T, Mirzayans F, Dubois S, Kume T, Parlee M, Ritch R, Koop B, Kuo WL, Collins C, Marshall J, Gould DB, Pearce W, Carlsson P, Enerbäck S, Morissette J, Bhattacharya S, Hogan B, Raymond V, Walter MA. Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. Am J Hum Genet. 1998;63:1316–28.

    Article  PubMed  CAS  Google Scholar 

  8. Du J, Li L, Ou Z, Kong C, Zhang Y, Dong Z, Zhu S, Jiang H, Shao Z, Huang B, Lu J. FOXC1, a target of polycomb, inhibits metastasis of breast cancer cells. Breast Cancer Res Treat. 2012;131:65–73.

    Article  PubMed  CAS  Google Scholar 

  9. Chung TK, Lau TS, Cheung TH, Yim SF, Lo KW, Siu NS, Chan LK, Yu MY, Kwong J, Doran G, Barroilhet LM, Ng AS, Wong RR, Wang VW, Mok SC, Smith DI, Berkowitz RS, Wong YF. Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1. Int J Cancer. 2012;130:1036–45. doi:10.1002/ijc.26060.

    Article  PubMed  CAS  Google Scholar 

  10. Ray PS, Wang J, Qu Y, Sim MS, Shamonki J, Bagaria SP, Ye X, Liu B, Elashoff D, Hoon DS, Walter MA, Martens JW, Richardson AL, Giuliano AE, Cui X. FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer Res. 2010;70:3870–6. doi:10.1158/0008-5472.

    Article  PubMed  CAS  Google Scholar 

  11. Bloushtain-Qimron N, Yao J, Snyder EL, Shipitsin M, Campbell LL, Mani SA, Hu M, Chen H, Ustyansky V, Antosiewicz JE, Argani P, Halushka MK, Thomson JA, Pharoah P, Porgador A, Sukumar S, Parsons R, Richardson AL, Stampfer MR, Gelman RS, Nikolskaya T, Nikolsky Y, Polyak K. Cell type-specific DNA methylation patterns in the human breast. Proc Natl Acad Sci U S A. 2008;105:14076–81. doi:10.1073/pnas.0805206105.

    Article  PubMed  CAS  Google Scholar 

  12. Wang J, Ray PS, Sim MS, Zhou XZ, Lu KP, Lee AV, Lin X, Bagaria SP, Giuliano AE, Cui X. FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling. Oncogene. 2012;31:4798–802. doi:10.1038/onc.2011.635.

    Article  PubMed  CAS  Google Scholar 

  13. Ray PS, Bagaria SP, Wang J, Shamonki JM, Ye X, Sim MS, Steen S, Qu Y, Cui X, Giuliano AE. Basal-like breast cancer defined by FOXC1 expression offers superior prognostic value: a retrospective immunohistochemical study. Ann Surg Oncol. 2011;18:3839–47.

    Article  PubMed  Google Scholar 

  14. Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, Rosen JM, Weinberg RA, Mani SA. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci U S A. 2010;107(35):15449–54. doi:10.1073/pnas.1004900107.

    Article  PubMed  CAS  Google Scholar 

  15. Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S, Wang Q, Chia D, Goodglick L, Kurdistani SK. Global levels of histone modifications predict prognosis in different cancers. Am J Pathol. 2009;174:1619–28. doi:10.2353/ajpath.2009.080874.

    Article  PubMed  CAS  Google Scholar 

  16. Piperi C, Vlastos F, Farmaki E, Martinet N, Papavassiliou AG. Epigenetic effects of lung cancer predisposing factors impact on clinical diagnosis and prognosis. J Cell Mol Med. 2008;12:1495–501. doi:10.1111/j.1582-4934.2008.00309.x.

    Article  PubMed  CAS  Google Scholar 

  17. Yang S. Histone lysine demethylases: emerging roles in development, physiology and disease. Nat Rev Genet. 2007;8:829–33. doi:10.1038/nrg2218.

    Article  Google Scholar 

  18. Risch A, Plass C. Lung cancer epigenetics and genetics. Int J Cancer. 2008;123:1–7. doi:10.1002/ijc.23605.

    Article  PubMed  CAS  Google Scholar 

  19. **a L, Huang W, Tian D, Zhu H, Qi X, Chen Z, Zhang Y, Hu H, Fan D, Nie Y, Wu K. Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma. Hepatology. 2012. doi:10.1002/hep.26029.

  20. Peraldo-Neia C, Migliardi G, Mello-Grand M, Montemurro F, Segir R, Pignochino Y, Cavalloni G, Torchio B, Mosso L, Chiorino G, Aglietta M. Epidermal growth factor receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer. BMC Cancer. 2011;11:31. doi:10.1186/1471-2407-11-31.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of General Surgery, First People’s Hospital of Changshu City, Changshu Hospital Affiliated to Soochow University, Changshu, 215500, Jiangsu Province, China

    Lei Wang & Feng Gu

  2. Department of Oncology, Wuxi People’s Hospital Affiliated to Nan**g Medical University, No.299, Qingyang Road, Wuxi, 214023, China

    Chao-Ying Liu, Run-Jie Wang, Jiang Li & Jun-Ying Xu

Authors
  1. Lei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao-Ying Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Run-Jie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun-Ying Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun-Ying Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, L., Gu, F., Liu, CY. et al. High level of FOXC1 expression is associated with poor prognosis in pancreatic ductal adenocarcinoma. Tumor Biol. 34, 853–858 (2013). https://doi.org/10.1007/s13277-012-0617-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0617-7

Keywords

Search

Navigation