Skip to main content

Advertisement

SpringerLink
Log in

Krüppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Krüppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR, Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial-mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC. The relationship between KLF8 expression and various clinicopathological features or EMT markers was investigated. The results showed m-RNA and protein of KLF8 were overexpressed in NSCLC and the percent of KLF8 positive cells was positively correlated with TNM stage, lymph node metastasis and poor overall survive. Moreover, high expression of KLF8 correlated with E-cadherin low expression, and Vimentin overexpression. Additionally, COX multivariate regression analysis suggested that TNM stage, KLF8, E-cadherin and Vimentin were independent prognostic indicators for overall survival of patients with NSCLC. The data demonstrate that KLF8 is overexpressed in NSCLC. KLF8 overexpression promotes the malignancy of NSCLC, which mechanism may be involved in EMT. KLF8 maybe serve as a potential therapeutic target for NSCLC.

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

Access this article

Log in via an institution

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 et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics. CA Cancer J Clin 62(1):10–29

    Article  Google Scholar 

  3. Gao W et al (2011) Circulating microRNAs: possible prediction biomarkers for personalized therapy of non-small-cell lung carcinoma. Clin Lung Cancer 12(1):14–17

    Article  CAS  PubMed  Google Scholar 

  4. Smith CB, Kelley AS, Meier DE (2010) Evidence for new standard of care in non-small cell lung cancer patients. Semin Thorac Cardiovasc Surg 22(3):193–194

    Article  PubMed  Google Scholar 

  5. Pearson R et al (2008) Kruppel-like transcription factors: a functional family. Int J Biochem Cell Biol 40(10):1996–2001

    Article  CAS  PubMed  Google Scholar 

  6. Zhao J et al (2003) Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. Mol Cell 11(6):1503–1515

    Article  CAS  PubMed  Google Scholar 

  7. Wang X, Zhao J (2007) KLF8 transcription factor participates in oncogenic transformation. Oncogene 26(3):456–461

    Article  CAS  PubMed  Google Scholar 

  8. Quadrini KJ, Bieker JJ (2002) Kruppel-like zinc fingers bind to nuclear import proteins and are required for efficient nuclear localization of erythroid Kruppel-like factor. J Biol Chem 277(35):32243–32252

    Article  CAS  PubMed  Google Scholar 

  9. van Vliet J, Turner J, Crossley M (2000) Human Kruppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription. Nucleic Acids Res 28(9):1955–1962

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wang X et al (2007) Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Res 67(15):7184–7193

    Article  CAS  PubMed  Google Scholar 

  11. Wang X et al (2008) Activation of KLF8 transcription by focal adhesion kinase in human ovarian epithelial and cancer cells. J Biol Chem 283(20):13934–13942

    Article  CAS  PubMed  Google Scholar 

  12. Wang X et al (2011) KLF8 promotes human breast cancer cell invasion and metastasis by transcriptional activation of MMP9. Oncogene 30(16):1901–1911

    Article  CAS  PubMed  Google Scholar 

  13. Fu WJ et al (2010) Small interference RNA targeting Kruppel-like factor 8 inhibits the renal carcinoma 786-0 cells growth in vitro and in vivo. J Cancer Res Clin Oncol 136(8):1255–1265

    Article  CAS  PubMed  Google Scholar 

  14. Yang T et al (2012) Kruppel-like factor 8 is a new Wnt/beta-catenin signaling target gene and regulator in hepatocellular carcinoma. PLoS One 7(6):e39668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li JC et al (2010) Up-regulation of Kruppel-like factor 8 promotes tumor invasion and indicates poor prognosis for hepatocellular carcinoma. Gastroenterology 139(6):2146–2157 e12

    Article  CAS  PubMed  Google Scholar 

  16. Liu L et al (2012) Lentivirus-delivered Kruppel-like factor 8 small interfering RNA inhibits gastric cancer cell growth in vitro and in vivo. Tumour Biol 33(1):53–61

    Article  CAS  PubMed  Google Scholar 

  17. Wang WF et al (2013) Kruppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer. World J Gastroenterol 19(27):4309–4315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454

    Article  CAS  Google Scholar 

  19. Iwatsuki M et al (2010) Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci 101(2):293–299

    Article  CAS  PubMed  Google Scholar 

  20. Thiery JP et al (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139(5):871–890

    Article  CAS  Google Scholar 

  21. Goldstraw P (2009) The 7th Edition of TNM in Lung Cancer: what now? J Thorac Oncol 4(6):671–673

    Article  PubMed  Google Scholar 

  22. Tischler V et al (2011) L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer. Mol Cancer 10:127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tamura M et al (2005) Prognostic significance of dysadherin expression in patients with non-small cell lung cancer. J Thorac Cardiovasc Surg 130(3):740–745

    Article  CAS  PubMed  Google Scholar 

  24. Maeda J et al (2008) Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy. Br J Cancer 98(3):596–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Richardson F et al (2012) The evaluation of E-Cadherin and vimentin as biomarkers of clinical outcomes among patients with non-small cell lung cancer treated with erlotinib as second- or third-line therapy. Anticancer Res 32(2):537–552

    CAS  PubMed  Google Scholar 

  26. Chikaishi Y, Uramoto H, Tanaka F (2011) The EMT status in the primary tumor does not predict postoperative recurrence or disease-free survival in lung adenocarcinoma. Anticancer Res 31(12):4451–4456

    PubMed  Google Scholar 

  27. Soltermann A et al (2008) Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res 14(22):7430–7437

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Jianchao Li and Yifei Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic surgery, the First People’s Hospital of Yancheng, 166 Yulongxi Road, Yancheng, Jiangsu, 224006, China

    Jianchao Li & Wenyi Wang

  2. Department of Thoracic surgery, the Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China

    Jianchao Li, Jianhua Xue, Mingming Xu & Junhua Liu

  3. Department of Pathology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China

    Yifei Liu & Jianguo Zhang

Authors
  1. Jianchao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yifei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianhua Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mingming Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jianguo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junhua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wenyi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Junhua Liu or Wenyi Wang.

Ethics declarations

Conflict of Interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Liu, Y., Xue, J. et al. Krüppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer. Pathol. Oncol. Res. 25, 115–121 (2019). https://doi.org/10.1007/s12253-017-0321-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-017-0321-4

Keywords

Search

Navigation