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: Heather Ann Brauer, Monica D'Arcy, Tanya E Libby, Henry J Thompson, Yutaka Y Yasui, Nobuyuki Hamajima, Christopher I Li, Melissa A Troester, Paul D Lampe
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 144 Issue 2 Pg. 299-306 (Apr 2014) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 24562771 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• Dermcidins
• Methylnitrosourea

Topics

• Adenocarcinoma (metabolism, pathology)
• Adult
• Aged
• Animals
• Biomarkers, Tumor (biosynthesis, blood)
• Breast Neoplasms (blood, pathology)
• Dermcidins (biosynthesis, blood)
• Disease Progression
• Female
• Humans
• Mammary Neoplasms, Experimental (chemically induced, metabolism, pathology)
• Methylnitrosourea
• Middle Aged
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)