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. 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.