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Clinical and Translational Oncology

, Volume 16, Issue 3, pp 307–314 | Cite as

Overexpressed transcription factor FOXM1 is a potential diagnostic and adverse prognostic factor in postoperational gastric cancer patients

  • X. Li
  • W. Qi
  • R. Yao
  • D. Tang
  • J. LiangEmail author
Research Article

Abstract

Purpose

In the present study, we intend to detect the expression of Forkhead box transcription (FOXM1) in gastric cancer tissues and cell lines, and analyze the correlation between FOXM1 expression and clinic-pathological features as well as their association with clinic outcomes in patients with resectable gastric cancers.

Methods

We examined the expression of FOXM1 in 103 cancer tissues from patients who underwent gastrectomy during Jan 2007 to Nov 2007 and 68 randomly selected para-cancer tissues by immunohistochemistry. The expression of FOXM1 protein in the benign and malignant human gastric cell lines was simultaneously detected using Western blot analysis. Data on clinic-pathological features and relevant prognostic factors in these patients were then analyzed.

Results

FOXM1 expression was absolutely higher in gastric cancer than para-cancer tissues (P < 0.001) and normal gastric epithelium cell lines (P = 0.022). No significant association was found between FOXM1 expression and any clinic-pathological parameters (P > 0.1). FOXM1 amplification was showed to be independently associated with prognosis in gastric cancer patients (P = 0.001), and its affection is more significant in patients with tumor size larger than 5 cm (P = 0.004), pT3–4 (P = 0.003) or pIII–IV (P = 0.001) as a result of stage-stratified analysis.

Conclusions

Overexpressed FOXM1 is a potential diagnostic and poor prognostic biomarker in postoperational gastric cancer patients.

Keywords

FOXM1 Diagnosis Prognosis Gastric cancer 

Notes

Acknowledgments

This study is supported by the grant of Medicine and Healthy Technology Development Program of Shandong Province (2011HZ028).

Conflict of interest

There is no conflict of interest for any of the authors in any aspect of the article.

References

  1. 1.
    Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L, et al. The incidences and mortalities of major cancers in China, 2009. Chin J Cancer. 2013;32:106–12.PubMedCrossRefGoogle Scholar
  2. 2.
    Wierstra I, Alves J. FOXM1, a typical proliferation-associated transcription factor. Biol Chem. 2007;388:1257–74.PubMedGoogle Scholar
  3. 3.
    Ma RY, Tong TH, Leung WY, Yao KM. Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1. Methods Mol Biol. 2010;647:113–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Katoh Y, Katoh M. Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med. 2009;9:873–86.PubMedCrossRefGoogle Scholar
  5. 5.
    Wang IC, Chen YJ, Hughes D, Petrovic V, Major ML, Park HJ, et al. Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase. Mol Cell Biol. 2005;25:10875–94.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Costa RH. FoxM1 dances with mitosis. Nat Cell Biol. 2005;7:108–10.PubMedCrossRefGoogle Scholar
  7. 7.
    He SY, Shen HW, Xu L, Zhao XH, Yuan L, Niu G, et al. FOXM1 promotes tumor cell invasion and correlates with poor prognosis in early-stage cervical cancer. Gynecol Oncol. 2012;127:601–10.PubMedCrossRefGoogle Scholar
  8. 8.
    Xia L, Huang W, Tian D, Zhu H, Zhang Y, Hu H, et al. Upregulated FoxM1 expression induced by hepatitis B virus X protein promotes tumor metastasis and indicates poor prognosis in hepatitis B virus-related hepatocellular carcinoma. J Hepatol. 2012;57:600–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Okada K, Fujiwara Y, Takahashi T, Nakamura Y, Takiguchi S, Nakajima K, et al. Overexpression of forkhead box M1 transcription factor (FOXM1) is a potential prognostic marker and enhances chemoresistance for docetaxel in gastric cancer. Ann Surg Oncol. 2013;20:1035–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, et al. FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 2006;66:3593–602.PubMedCrossRefGoogle Scholar
  11. 11.
    Yau C, Wang Y, Zhang Y, Foekens JA, Benz CC. Young age, increased tumor proliferation and FOXM1 expression predict early metastatic relapse only for endocrine-dependent breast cancers. Breast Cancer Res Treat. 2011;126:803–10.PubMedCrossRefGoogle Scholar
  12. 12.
    Xu N, Zhang X, Wang X, Ge HY, Wang XY, Garfield D, et al. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells. Acta Pharmacol Sin. 2012;33:675–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Carr JR, Park HJ, Wang Z, Kiefer MM, Raychaudhuri P. FoxM1 mediates resistance to herceptin and paclitaxel. Cancer Res. 2010;70:5054–63.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Kwok JM, Peck B, Monteiro LJ, Schwenen HD, Millour J, Coombes RC, et al. FOXM1 confers acquired cisplatin resistance in breast cancer cells. Mol Cancer Res. 2010;8:24–34.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Li Q, Zhang N, Jia Z, Le X, Dai B, Wei D, et al. Critical role and regulation of transcription factor FoxM1 in human gastric cancer angiogenesis and progression. Cancer Res. 2009;69:3501–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Remmele W, Stegner HE. Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987;8:138–40.PubMedGoogle Scholar
  17. 17.
    Halon A, Donizy P, Biecek P, Rudno-Rudzinska J, Kielan W, Matkowski R. HER-2 expression in immunohistochemistry has no prognostic significance in gastric cancer patients. ScientificWorldJournal. 2012;2012:941259.PubMedCrossRefGoogle Scholar
  18. 18.
    Kaestner KH, Knochel W, Martinez DE. Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev. 2000;14:142–6.PubMedGoogle Scholar
  19. 19.
    Xu N, Wu SD, Wang H, Wang Q, Bai CX. Involvement of FoxM1 in non-small cell lung cancer recurrence. Asian Pac J Cancer Prev. 2012;13:4739–43.PubMedCrossRefGoogle Scholar
  20. 20.
    Chen CH, Chien CY, Huang CC, Hwang CF, Chuang HC, Fang FM, et al. Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity. Oncogene. 2009;28:2723–37.PubMedCrossRefGoogle Scholar
  21. 21.
    Wang Z, Banerjee S, Kong D, Li Y, Sarkar FH. Down-regulation of Forkhead Box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells. Cancer Res. 2007;67:8293–300.PubMedCrossRefGoogle Scholar
  22. 22.
    Zu H, Wang F, Ma Y, Xue Y. Stage-stratified analysis of prognostic significance of tumor size in patients with gastric cancer. PLoS One. 2013;8:e54502.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Xiang HL, Liu F, Quan MF, Cao JG, Lv Y. 7-difluoromethoxyl-5,4′-di-n-octylgenistein inhibits growth of gastric cancer cells through downregulating forkhead box M1. World J Gastroenterol. 2012;18:4618–26.PubMedCrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2013

Authors and Affiliations

  1. 1.Department of Oncology of the Affiliated Hospital of Medical College Qingdao UniversityQingdaoChina
  2. 2.Central Laboratory of the Affiliated Hospital of Medical College Qingdao UniversityQingdaoChina
  3. 3.Thoracic Surgery of the Affiliated Hospital of Medical College Qingdao UniversityQingdaoChina

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