Clinical Research Papers:
Prognostic value of a 92-probe signature in breast cancer
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Salima Akter1, Tae Gyu Choi1, Minh Nam Nguyen1, Abel Matondo1, Jin-Hwan Kim1, Yong Hwa Jo1, Ara Jo1, Muhammad Shahid1, Dae Young Jun1, Ji Youn Yoo1, Ngoc Ngo Yen Nguyen1, Seong-Wook Seo1, Liaquat Ali2, Ju-Seog Lee3, Kyung-Sik Yoon1, Wonchae Choe1, Insug Kang1, Joohun Ha1, Jayoung Kim4, Sung Soo Kim1
1Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
2Department of Biochemistry and Cell Biology, Bangladesh University of Health Sciences, Dhaka, Bangladesh
3Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Sung Soo Kim, e-mail: [email protected]
Keywords: microarray, gene signature, breast cancer, prognosis
Received: December 26, 2014 Accepted: March 10, 2015 Published: April 11, 2015
Clinical applications of gene expression signatures in breast cancer prognosis still remain limited due to poor predictive strength of single training datasets and appropriate invariable platforms. We proposed a gene expression signature by reducing baseline differences and analyzing common probes among three recent Affymetrix U133 plus 2 microarray data sets. Using a newly developed supervised method, a 92-probe signature found in this study was associated with overall survival. It was robustly validated in four independent data sets and then repeated on three subgroups by incorporating 17 breast cancer microarray datasets. The signature was an independent predictor of patients’ survival in univariate analysis [(HR) 1.927, 95% CI (1.237–3.002); p < 0.01] as well as multivariate analysis after adjustment of clinical variables [(HR) 7.125, 95% CI (2.462–20.618); p < 0.001]. Consistent predictive performance was found in different multivariate models in increased patient population (p = 0.002). The survival signature predicted a late metastatic feature through 5-year disease free survival (p = 0.006). We identified subtypes within the lymph node positive (p < 0.001) and ER positive (p = 0.01) patients that best reflected the invasive breast cancer biology. In conclusion using the Common Probe Approach, we present a novel prognostic signature as a predictor in breast cancer late recurrences.
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