Dermcidin expression is associated with disease progression and survival among breast cancer patients

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• 作者：Heather Ann Brauer (1) (2) (3)
  Monica D’Arcy (3)
  Tanya E. Libby (2)
  Henry J. Thompson (4)
  Yutaka Y. Yasui (5)
  Nobuyuki Hamajima (6)
  Christopher I. Li (2)
  Melissa A. Troester (3) (7) (8)
  Paul D. Lampe (1) (2)
  
• 关键词：Dermcidin ; Breast cancer ; Serum ; Microenvironment
• 刊名：Breast Cancer Research and Treatment
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：144
• 期：2
• 页码：299-306
• 全文大小：298 KB
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• 作者单位：Heather Ann Brauer (1) (2) (3)
  Monica D’Arcy (3)
  Tanya E. Libby (2)
  Henry J. Thompson (4)
  Yutaka Y. Yasui (5)
  Nobuyuki Hamajima (6)
  Christopher I. Li (2)
  Melissa A. Troester (3) (7) (8)
  Paul D. Lampe (1) (2)
  
  1. Molecular and Cellular Biology Program, University of Washington, Seattle, WA, 98195, USA
  2. Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA
  3. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
  4. Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO, 80523, USA
  5. School of Public Health, University of Alberta, Edmonton, AB, T6G 1C9, Canada
  6. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanakoden, Chikusa-ku, Nagoya, 464-8681, Japan
  7. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
  8. Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
  
• ISSN：1573-7217

文摘

Improved diagnostic screening has led to earlier detection of many tumors, but screening may still miss many aggressive tumor types. Proteomic and genomic profiling studies of breast cancer samples have identified tumor markers that may help improve screening for more aggressive, rapidly growing breast cancers. To identify potential blood-based biomarkers for the early detection of breast cancer, we assayed serum samples via matrix-assisted laser desorption ionization–time of flight mass spectrometry from a rat model of mammary carcinogenesis. We found elevated levels of a fragment of the protein dermcidin (DCD) to be associated with early progression of N-methylnitrosourea-induced breast cancer, demonstrating significance at weeks 4 (p?=?0.045) and 5 (p?=?0.004), a time period during which mammary pathologies rapidly progress from ductal hyperplasia to adenocarcinoma. The highest serum concentrations were observed in rats bearing palpable mammary carcinomas. Increased DCD was also detected with immunoblotting methods in 102 serum samples taken from women just prior to breast cancer diagnosis. To validate these findings in a larger population, we applied a 32-gene in vitro DCD response signature to a dataset of 295 breast tumors and assessed correlation with intrinsic breast cancer subtypes and overall survival. The DCD-derived gene signature was significantly associated with subtype (p?<?0.001) and poorer overall survival [HR (95?% CI)?=?1.60 (1.01-.51), p?=?0.044]. In conclusion, these results present novel evidence that DCD levels may increase in early carcinogenesis, particularly among more aggressive forms of breast cancer.