Breast Cancer

, Volume 24, Issue 2, pp 326–335

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

  • Takuya Nagata
  • Yutaka Shimada
  • Shinichi Sekine
  • Makoto Moriyama
  • Isaya Hashimoto
  • Koshi Matsui
  • Tomoyuki Okumura
  • Takashi Hori
  • Johji Imura
  • Kazuhiro Tsukada
Original Article



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.


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.


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.


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.


Breast cancer NANOG KLF4 



Triple-negative breast cancer


Small interfering RNA


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Copyright information

© The Japanese Breast Cancer Society 2016

Authors and Affiliations

  • Takuya Nagata
    • 1
  • Yutaka Shimada
    • 2
  • Shinichi Sekine
    • 1
  • Makoto Moriyama
    • 1
  • Isaya Hashimoto
    • 1
  • Koshi Matsui
    • 1
  • Tomoyuki Okumura
    • 1
  • Takashi Hori
    • 3
  • Johji Imura
    • 3
  • Kazuhiro Tsukada
    • 1
  1. 1.Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for ResearchUniversity of ToyamaToyamaJapan
  2. 2.Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  3. 3.Department of Pathology, Graduate School of Research Into Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan

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