title: Dermcidin expression is associated with disease progression and survival among breast cancer patients.
abstract: 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 (1.01-2.51), 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.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, WA, 98195, USA, habrauer@med.unc.edu.
authors.forename: Heather Ann
authors.initials: HA
authors.lastname: Brauer
authors.forename: Monica
authors.initials: M
authors.lastname: D'Arcy
authors.forename: Tanya E
authors.initials: TE
authors.lastname: Libby
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Thompson
authors.forename: Yutaka Y
authors.initials: YY
authors.lastname: Yasui
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Li
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D054805:Dermcidins / Q000096:biosynthesis* / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008770:Methylnitrosourea; D008875:Middle Aged; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D054805:Dermcidins; D008770:Methylnitrosourea