Takuya Nagata1, Yutaka Shimada2, Shinichi Sekine3, Makoto Moriyama3, Isaya Hashimoto3, Koshi Matsui3, Tomoyuki Okumura3, Takashi Hori4, Johji Imura4, Kazuhiro Tsukada3. 1. 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. 2. Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. 3. Department of Surgery and Science, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. 4. Department of Pathology, Graduate School of Research Into Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
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.
BACKGROUND: Prognosis of breast cancerpatients 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.
Authors: Melyssa S Roberts; Lindsey J Anstine; Viviane S Finke; Benjamin L Bryson; Bryan M Webb; Kristen L Weber-Bonk; Darcie D Seachrist; Parth R Majmudar; Ruth A Keri Journal: Breast Cancer Res Date: 2020-06-18 Impact factor: 6.466
Authors: Agnieszka Taracha-Wisniewska; Grzegorz Kotarba; Sebastian Dworkin; Tomasz Wilanowski Journal: Int J Mol Sci Date: 2020-11-22 Impact factor: 5.923