Skip to main content

Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer

Tumor Biology volume 34, pages 2605–2609 (2013)Cite this article

Abstract

Altered expression of forkhead box Q1 (FOXQ1) is observed in various types of human cancers. However, the clinical significance of FOXQ1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of FOXQ1 in GC. FOXQ1 messenger RNA (mRNA) and protein expression were determined by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot in 20 pairs of fresh frozen GC tissues and corresponding noncancerous tissues. Additionally, FOXQ1 expression was analyzed by immunohistochemistry in 158 clinicopathologically characterized GC cases. The correlation of FOXQ1 expression with patients’ survival rate was assessed by Kaplan–Meier and Cox regression. Our results showed that the expression levels of FOXQ1 mRNA and protein in GC tissues were both significantly higher than those in non-cancerous tissues. Our results showed that the high expression of FOXQ1 in GC was related to tumor size (P = 0.026), histological grade (P = 0.021), lymph node involvement (P = 0.002), and tumor–node–metastasis stage (P = 0.028). Kaplan–Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. Furthermore, Cox multivariates analysis indicated that FOXQ1 expression level was an independent prognostic factor for the overall survival rate of GC patients. In conclusion, overexpression of FOXQ1 is closely related to progression of GC and might be regarded as an independent predictor of poor prognosis for GC.

This is a preview of subscription content, access via your institution.

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

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  2. Jackson C, Cunningham D, Oliveira J, ESMO Guidelines Working Group. Gastric cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20:34–6.

    Article  PubMed  Google Scholar 

  3. Overdier DG, Porcella A, Costa RH. The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Mol Cell Biol. 1994;14:2755–66.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  4. Hoggatt AM, Kriegel AM, Smith AF, Herring BP. Hepatocyte nuclear factor-3 homologue 1 (HFH-1) represses transcription of smooth muscle-specific genes. J Biol Chem. 2000;275:31162–70. doi:10.1074/jbc.M005595200.

    CAS  Article  PubMed  Google Scholar 

  5. Feuerborn A, Srivastava PK, Küffer S, Grandy WA, Sijmonsma TP, Gretz N, et al. The Forkhead factor FoxQ1 influences epithelial differentiation. J Cell Physiol. 2011;226:710–9. doi:10.1002/jcp.22385.

    CAS  Article  PubMed  Google Scholar 

  6. Jonsson H, Peng SL. Forkhead transcription factors in immunology. Cell Mol Life Sci. 2005;62:397–409.

    CAS  Article  PubMed  Google Scholar 

  7. Kaneda H, Arao T, Tanaka K, Tamura D, Aomatsu K, Kudo K, et al. FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth. Cancer Res. 2010;70:2053–63. doi:10.1158/0008-5472.CAN-09-2161.

    CAS  Article  PubMed  Google Scholar 

  8. Zhu Z, Zhu Z, Pang Z, Xing Y, Wan F, Lan D, et al. Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer. Int J Oncol. 2013;42:1271–8. doi:10.3892/ijo.2013.1807.

    CAS  PubMed  Google Scholar 

  9. Qiao Y, Jiang X, Lee ST, Karuturi RK, Hooi SC, Yu Q. FOXQ1 regulates epithelial–mesenchymal transition in human cancers. Cancer Res. 2011;71(8):3076–86. doi:10.1158/0008-5472.CAN-10-2787.

    CAS  Article  PubMed  Google Scholar 

  10. Zhang H, Meng F, Liu G, Zhang B, Zhu J, Wu F, et al. Forkhead transcription factor foxq1 promotes epithelial–mesenchymal transition and breast cancer metastasis. Cancer Res. 2011;71(4):1292–301. doi:10.1158/0008-5472.CAN-10-2825.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  11. Bieller A, Pasche B, Frank S, Gläser B, Kunz J, Witt K, et al. Isolation and characterization of the human forkhead gene FOXQ1. DNA Cell Biol. 2001;20:555–61. doi:10.1089/104454901317094963.

    CAS  Article  PubMed  Google Scholar 

  12. Feng J, Zhang X, Zhu H, Wang X, Ni S, Huang J. FoxQ1 overexpression influences poor prognosis in non-small cell lung cancer, associates with the phenomenon of EMT. PLoS One. 2012;7:e39937. doi:10.1371/journal.pone.0039937.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  13. Huang J, Zhu H, Wang X, Tang Q, Huang H, Wu K, et al. The patterns and expression of KDR in normal tissues of human internal organs. J Mol Histol. 2011;42:597–603. doi:10.1007/s10735-011-9355-1.

    CAS  Article  PubMed  Google Scholar 

  14. Li W, Yu CP, Xia JT, Zhang L, Weng GX, Zheng HQ, et al. Sphingosine kinase 1 is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 2009;15:1393–9. doi:10.1158/1078-0432.CCR-08-1158.

    CAS  Article  PubMed  Google Scholar 

  15. 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.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (nos. 81272516, 81090270, 81090273, 30900674, 30973428, 81101504, 81000937, and 31071135).

Conflicts of interest

None

Author information

Affiliations

  1. State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127 Changle Western Rd., Xi’an, 710032, Shaanxi Province, China

    Shu-Hui Liang, Biao-Luo Wang, Hai-Feng Jin, Li-Ping Yao, Ya-Ni Li, Min Chen, Yong-Zhan Nie, Xin Wang, Xue-Gang Guo, Kai-Chun Wu, Jie Ding & Dai-Ming Fan

  2. The Second Affiliated Hospital, Xi’an Medical University, Xi’an, 710038, Shaanxi Province, China

    Xi-Zhang Yan

Authors
  1. Shu-Hui Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xi-Zhang Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Biao-Luo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hai-Feng Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Ping Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ya-Ni Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Min Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yong-Zhan Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xue-Gang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kai-Chun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jie Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Dai-Ming Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kai-Chun Wu or Jie Ding.

Additional information

S.-H. Liang, X.-Z. Yan, and B.-L. Wang contributed equally to this work.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Liang, SH., Yan, XZ., Wang, BL. et al. Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer. Tumor Biol. 34, 2605–2609 (2013). https://doi.org/10.1007/s13277-013-0808-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-0808-x

Keywords

  • FOXQ1
  • Prognosis
  • Gastric caner