Prognostic significance of NANOG and KLF4 for breast cancer
ABSTRACT BACKGROUND: Some of the induced pluripotent stem cell (iPS cell)-inducing factors have been reported to be expressed in breast cancer. The aim of the present study was to examine the relationship between the expression of iPS cell-inducing factors and the prognosis of breast cancer patients. METHODS: In 100 breast cancer patients, the expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 was determined by immunohistochemistry using a tissue microarray analysis. RESULTS: Patients with strong expression of NANOG had significantly lower disease-free survival (DFS) and overall survival rates than those with weak expression of NANOG (P = 0.004 and 0.033, respectively). In contrast, patients with strong expression of KLF4 had better DFS (P = 0.014). CONCLUSIONS: Strong expression of NANOG is an indicator of a poor prognosis for breast cancer patients, whereas KLF4 is a favorable prognostic indicator. Our results suggest that NANOG stimulates the growth and metastasis of breast cancer cells, whereas KLF4 inhibits these processes.
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- "Nasopharyngeal cancer Clinical prognosis Wang et al. (2012) Melanoma Cell invasion Girouard et al. (2012) Colon cancer Cell invasion and metastases Neumann et al. (2011) Osteosarcomas Survival and self-renewal Basu-Roy et al. (2012) Gastric cancer Matsuoka et al. (2012) Lung cancer Transformation Chen et al. (2012) Prostate cancer Jia et al. (2011b) Breast cancer Stolzenburg et al. (2012) Oct4 Gastric cancer Negative prognostic factor Matsuoka et al. (2012) Oral squamous cell carcinoma Chiou et al. (2008) and Tsai et al. (2011) Klf4 Breast cancer Good prognosis Nagata et al. (2012) Leukemias Different Klf4 mRNA levels mirror differentiation state, not a prognostic factor Guo and Tang (2012) Squamous cell carcinoma Poor prognosis Chen et al. (2008) Breast cancer Rowland et al. (2005) Nanog Hepatocellular carcinoma Shan et al. (2012) Breast cancer Poor prognosis Nagata et al. (2012) Oral squamous cell carcinoma (OSCC) (Nanog/Oct-4/CD133 coexpression) Poor prognosis Chiou et al. (2008) Continued oncogenes such as c-Myc in epithelial tumors is sufficient to reactivate an ES cell-like transcriptional signature. Other reprogramming factors, such as Sox2 and Lin28, have been documented as oncogenes in small cell lung and esophageal squamous-cell carcinomas and germ-cell tumors (Bass et al., 2009; West et al., 2009). "
ABSTRACT: Rapid progress made in various areas of regenerative medicine in recent years occurred both at the cellular level, with the Nobel prize-winning discovery of reprogramming (generation of induced pluripotent stem (iPS) cells) and also at the biomaterial level. The use of four transcription factors, Oct3/4, Sox2, c-Myc, and Klf4 (called commonly "Yamanaka factors") for the conversion of differentiated cells, back to the pluripotent/embryonic stage, has opened virtually endless and ethically acceptable source of stem cells for medical use. Various types of stem cells are becoming increasingly popular as starting components for the development of replacement tissues, or artificial organs. Interestingly, many of the transcription factors, key to the maintenance of stemness phenotype in various cells, are also overexpressed in cancer (stem) cells, and some of them may find the use as prognostic factors. In this review, we describe various methods of iPS creation, followed by overview of factors known to interfere with the efficiency of reprogramming. Next, we discuss similarities between cancer stem cells and various stem cell types. Final paragraphs are dedicated to interaction of biomaterials with tissues, various adverse reactions generated as a result of such interactions, and measures available, that allow for mitigation of such negative effects.International review of cell and molecular biology 01/2014; 308:167-203. DOI:10.1016/B978-0-12-800097-7.00005-1 · 4.52 Impact Factor
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ABSTRACT: Cancer stem cell-like cells (CSCs) are cancer cells that have the ability of self-renewal and differentiation into multiple malignant cell types (hierarchy). Thus, can cause relapses and metastasis. CSCs' phenotype is defined by special transcription factors such as Nanog, Oct3/4, Sox2, Nestin, and CD34. The present study aims to determine the change in gene expression of the above markers in correlation with the stage of the disease in breast cancer patients. Initially, whole blood samples from patients with breast cancer were collected, followed by the isolation and culture of circulating tumor cells (CTCs). This was followed by the quantification of CSCs from the above cultures. CSCs' molecular analysis was performed with qPCR, with the use of gene specific primers. At the same time of the analysis, the clinical assessments of the patients were requested from their physicians. The results indicated a linear relationship between the gene expression of stemness markers and the stage of the disease, as well as specific expression patterns by stage. It seems that these genes have an important role in the progression of the disease, thus they might be target for new treatment approaches.Current Stem Cell Research & Therapy 10/2012; 7. DOI:10.2174/157488812804484639 · 2.86 Impact Factor
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ABSTRACT: Prostate cancer (PCa) is a leading cause of mortality, and despite good response to androgen ablation this response is eventually lost. In the present study, androgen receptor (AR) expression and neuroendocrine differentiation (NED) were evaluated in hormone-sensitive (HSPC) and castration-resistant prostate cancers (CRPC). Prostate tissues were obtained from 20 HSPC patients at diagnosis and 28 CRPC patients at castration-resistant progression. AR, chromogranin A (CGA) and neuron-specific enolase (NSE) were evaluated by immunohistochemical staining (IHS) in representative positive cores for PCa. IHS intensity was graded as negative, 0; positive, 1+ and strongly positive, 2+. The proportion of the 1+ and 2+ areas in PCa cells was determined. PCa was considered to be in NED if ≥50% of the tumor cells were 1+ or 2+ for CGA or NSE. The observed IHS intensity (0/1+/2+) for AR, CGA and NSE was 0/4/16, 5/11/4 and 11/4/5 in HSPC patients and 9/3/16, 5/8/15 and 8/4/16 in CRPC patients, respectively. AR expression was positive in all the HSPC and 19/28 CRPC patients (P=0.0049). NED was observed in 9/20 HSPC and 20/28 CRPC patients (P=0.0649). NED was significantly associated with a negative AR expression in CRPC patients (P=0.0292). Multivariate analysis revealed that age, AR expression and strong NED were independent parameters for prognosis following castration-resistant progression. In conclusion, prostate biopsy following castration-resistant progression was necessary. AR was lost in a subset of CRPC. NED was observed more frequently in CRPC vs. HSPC and was associated with a worse prognosis.Molecular and Clinical Oncology 01/2013; 1(2):257-262. DOI:10.3892/mco.2013.69