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Decreased Kruppel-like factor 4 (KLF4) expression may correlate with poor survival in gastric adenocarcinoma

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Abstract

Kruppel-like factors (KLFs) play either anti- or pro-proliferation roles in different human cancers. Here, we investigated the expression of KLF4 in gastric cancers and its correlation with clinicopathological parameters and overall survival. KLF4 expression was measured in 118 surgical specimens by immunohistochemical microarray assay. No association of cytoplasmic KLF4 expression with gender, TNM status, stage, survival, and pathological type was found. Using Kaplan–Meier analysis, significantly higher overall survival rate was observed in patients with high cytoplasmic KLF4 expression compared to low cytoplasmic KLF4 expression. Univariate analysis revealed that cytoplasmic KLF4 expression, grade, histological type, lymph node metastasis, and stages were correlated to longer overall survival. Our results suggest that KLF4 may play an anti-oncogenic role in gastric tumorigenesis.

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References

  1. Black AR, Black JD, Azizkhan-Clifford J. Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol. 2001;188:143–60.

    Article  CAS  PubMed  Google Scholar 

  2. Kaczynski J, Cook T, Urrutia R. Sp1- and Kruppel-like transcription factors. Genome Biol. 2003;4:206.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Dang DT, Pevsner J, Yang VW. The biology of the mammalian Kruppel-like family of transcription factors. Int J Biochem Cell Biol. 2000;32:1103–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Feinberg MW, Cao Z, Wara AK, Lebedeva MA, Senbanerjee S, Jain MK. Kruppel-like factor 4 (KLF4) is a mediator of proinflammatory signaling in macrophages. J Biol Chem. 2005;280(46):38247–58.

    Article  CAS  PubMed  Google Scholar 

  5. Narla G, Friedman SL, Martignetti JA. Kruppel cripples prostate cancer: KLF6 progress and prospects. Am J Pathol. 2003;162:1047–52.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Dong JT. Chromosomal deletions and tumor suppressor genes in prostate cancer. Cancer Metastasis Rev. 2001;20:173–93.

    Article  CAS  PubMed  Google Scholar 

  7. Turner J, Crossley M. Basic Kruppel-like factor functions within a network of interacting haematopoietic transcription factors. Int J Biochem Cell Biol. 1999;31:1169–74.

    Article  CAS  PubMed  Google Scholar 

  8. Chen X, Johns DC, Geiman DE, et al. Kruppel-like factor 4 (gut-enriched Kruppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle. J Biol Chem. 2001;276:30423–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Chen X, Whitney EM, Gao SY, Yang VW. Transcriptional profiling of Kruppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation. J Mol Biol. 2003;326:665–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Shie JL, Chen ZY, O’Brien MJ, Pestell RG, Lee ME, Tseng CC. Role of gut-enriched Kruppel-like factor in colonic cell growth and differentiation. Am J Physiol Gastrointest Liver Physiol. 2000;279:G806–14.

    CAS  PubMed  Google Scholar 

  11. Ohnishi S, Ohnami S, Laub F, et al. Downregulation and growth inhibitory effect of epithelial-type Kruppel-like transcription factor KLF4, but not KLF5, in bladder cancer. Biochem Biophys Res Commun. 2003;308:251–6.

    Article  CAS  PubMed  Google Scholar 

  12. Xu J, Lu B, Xu F, et al. Dynamic down-regulation of Kruppel-like factor 4 in colorectal adenoma-carcinoma sequence. J Cancer Res Clin Oncol. 2008;134:891–8.

    Article  CAS  PubMed  Google Scholar 

  13. Wei D, Gong W, Kanai M, et al. Drastic down-regulation of Kruppel-like factor 4 expression is critical in human gastric cancer development and progression. Cancer Res. 2005;65:2746–54.

    Article  CAS  PubMed  Google Scholar 

  14. Yang WT, Zheng PS. Kruppel-like factor 4 function as a tumor suppressor in cervical carcinoma. Cancer. 2012;118:3691–702.

    Article  CAS  PubMed  Google Scholar 

  15. Patel NV, Ghaleb AM, Nandan MO, Yang VW. Expression of the tumor suppressor Kruppel-like factor 4 as a prognostic predictor for colon cancer. Cancer Epidemiol Biomarkers Prev. 2010;19:2631–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Hu R, Zuo Y, Zuo L, et al. KLF4 expression correlates with the degree of differentiation in colorectal cancer. Gut Liver. 2011;5:154–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Guan H, Xie L, Leithauser F, et al. KLF4 is a tumor suppressor in B-cell non-Hodgkin lymphoma and in classic Hodgkin lymphoma. Blood. 2010;116:1469–78.

    Article  CAS  PubMed  Google Scholar 

  18. Wei D, Kanai M, Jia Z, Le X, Xie K. Kruppel-like factor 4 induces p27Kip1 expression in and suppresses the growth and metastasis of human pancreatic cancer cells. Cancer Res. 2008;68:4631–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Shie JL, Chen ZY, Fu M, Pestell RG, Tseng CC. Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif. Nucleic Acids Res. 2000;28:2969–76.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Zhang W, Geiman DE, Shields JM, et al. The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter. J Biol Chem. 2000;275:18391–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Chen CJ, Hsu LS, Lin SH, et al. Loss of nuclear expression of Kruppel-like factor 4 is associated with poor prognosis in patients with oral cancer. Hum Pathol. 2012;43:1119–25.

    Article  CAS  PubMed  Google Scholar 

  22. Foster KW, Frost AR, McKie-Bell P, et al. Increase of GKLF messenger RNA and protein expression during progression of breast cancer. Cancer Res. 2000;60:6488–95.

    CAS  PubMed  Google Scholar 

  23. Pandya AY, Talley LI, Frost AR, et al. Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer. Clin Cancer Res. 2004;10:2709–19.

    Article  CAS  PubMed  Google Scholar 

  24. Chen YJ, Wu CY, Chang CC, Ma CJ, Li MC, Chen CM. Nuclear Kruppel-like factor 4 expression is associated with human skin squamous cell carcinoma progression and metastasis. Cancer Biol Ther. 2008;7:777–82.

    Article  CAS  PubMed  Google Scholar 

  25. Wei D, Wang L, Kanai M, et al. KLF4alpha up-regulation promotes cell cycle progression and reduces survival time of patients with pancreatic cancer. Gastroenterology. 2010;139:2135–45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Tai SK, Yang MH, Chang SY, et al. Persistent Kruppel-like factor 4 expression predicts progression and poor prognosis of head and neck squamous cell carcinoma. Cancer Sci. 2011;102:895–902.

    Article  CAS  PubMed  Google Scholar 

  27. Kanai M, Wei D, Li Q, et al. Loss of Kruppel-like factor 4 expression contributes to Sp1 overexpression and human gastric cancer development and progression. Clin Cancer Res. 2006;12:6395–402.

    Article  CAS  PubMed  Google Scholar 

  28. Katz JP, Perreault N, Goldstein BG, et al. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology. 2005;128:935–45.

    Article  CAS  PubMed  Google Scholar 

  29. Soon MS, Hsu LS, Chen CJ, et al. Expression of Kruppel-like factor 5 in gastric cancer and its clinical correlation in Taiwan. Virchows Arch. 2011;459:161–6.

    Article  CAS  PubMed  Google Scholar 

  30. Cho YG, Song JH, Kim CJ, et al. Genetic and epigenetic analysis of the KLF4 gene in gastric cancer. Apmis. 2007;115:802–8.

    Article  CAS  PubMed  Google Scholar 

  31. Collins LC, Botero ML, Schnitt SJ. Bimodal frequency distribution of estrogen receptor immunohistochemical staining results in breast cancer: an analysis of 825 cases. Am J Clin Pathol. 2005;123:16–20.

    Article  PubMed  Google Scholar 

  32. Pearson R, Fleetwood J, Eaton S, Crossley M, Bao S. Kruppel-like transcription factors: a functional family. Int J Biochem Cell Biol. 2008;40:1996–2001.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by Grant: 99-CCH-IRP-09 from Changhua Christian Hospital.

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We declare that we did not have conflict of interest.

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Correspondence to Kun-Tu Yeh or Maw-Soan Soon.

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Li-Sung Hsu and Chien-Pin Chan contributed equally to this work as first author.

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Hsu, LS., Chan, CP., Chen, CJ. et al. Decreased Kruppel-like factor 4 (KLF4) expression may correlate with poor survival in gastric adenocarcinoma. Med Oncol 30, 632 (2013). https://doi.org/10.1007/s12032-013-0632-6

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  • DOI: https://doi.org/10.1007/s12032-013-0632-6

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