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KLF4 and NANOG are prognostic biomarkers for triple-negative breast cancer

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Abstract

Background

Prognosis of breast cancer patients has been reported to depend on the expression of induced pluripotent stem (iPS) cell-inducing factors: KLF4 and NANOG. However, the relationship between KLF4 or NANOG expression in each breast cancer subtype and the life prognosis has not been elucidated.

Method

KLF4 and NANOG expression levels were evaluated in 208 patients using a newly developed tissue microarray (TMA). In vitro, siRNA against klf4 (siKLF4) was transfected in TNBC cell line MDA-MB-231, and the expression of KLF4 was inhibited.

Results

Triple-negative breast cancer (TNBC) patients in KLF4 high-expression (upper) group had more favorable overall survival (OS) and disease-free survival (DFS) rates than KLF4 lower group (p = 0.0453 and p = 0.0427). In contrast, patients in the NANOG upper group had significantly poorer prognosis than lower group in TNBC breast cancer subtypes (p < 0.0001). Multivariate analysis showed that KLF4 (p = 0.0313), NANOG (p = 0.0002), and TNM stage (p = 0.0001) are mutually independent prognostic factors. It was also shown that the proliferation and invasion ability of siKLF4-induced TNBC cells were up-regulated significantly.

Conclusion

Our findings suggested that KLF4 and NANOG expression levels were favorable prognostic factors for TNBC patients. KLF4 also had an ability to inhibit the proliferation and invasion of TNBC.

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Abbreviations

TNBC:

Triple-negative breast cancer

siRNA:

Small interfering RNA

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Acknowledgments

This work was supported by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (Monbusho).

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Takuya Nagata, Shinichi Sekine, Makoto Moriyama, Isaya Hashimoto, Koshi Matsui, Tomoyuki Okumura & Kazuhiro Tsukada

  2. Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

    Yutaka Shimada

  3. Department of Pathology, Graduate School of Research Into Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Takashi Hori & Johji Imura

Authors
  1. Takuya Nagata
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  2. Yutaka Shimada
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  3. Shinichi Sekine
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  10. Kazuhiro Tsukada
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Correspondence to Takuya Nagata.

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Nagata, T., Shimada, Y., Sekine, S. et al. KLF4 and NANOG are prognostic biomarkers for triple-negative breast cancer. Breast Cancer 24, 326–335 (2017). https://doi.org/10.1007/s12282-016-0708-1

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  • DOI: https://doi.org/10.1007/s12282-016-0708-1

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