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


METHODS
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.


CONCLUSIONS
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.
Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. naga0103@med.u-toyama.ac.jp.
Takuya
T
Nagata
Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Yutaka
Y
Shimada
Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Shinichi
S
Sekine
Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Makoto
M
Moriyama
Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Isaya
I
Hashimoto
Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Koshi
K
Matsui
Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Tomoyuki
T
Okumura
Department of Pathology, Graduate School of Research Into Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Takashi
T
Hori
Department of Pathology, Graduate School of Research Into Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Johji
J
Imura
Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Kazuhiro
K
Tsukada
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
D014408:Biomarkers, Tumor; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein
Breast cancer; KLF4; NANOG