Journal
PROTEOMICS CLINICAL APPLICATIONS
Volume 10, Issue 5, Pages 605-613Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.201500016
Keywords
2D LC/MS; Biomarkers; Breast cancer; Nipple discharge; Proteomics
Funding
- JSPS [22501030]
- Grants-in-Aid for Scientific Research [22501030] Funding Source: KAKEN
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Purpose: This research aimed to establish a diagnostic technique for breast cancer using nipple discharge (ND), with the objective of preventive diagnosis. ND has been proposed as a source of secreted proteomes that reflect early pathological changes in the ductal-lobular epithelial microenvironment, and could thus provide breast-specific cancer biomarkers that could be accessed noninvasively as a new clinical diagnostic technique. Experimental design: Minute amounts of ND from patients with and without breast cancer (n = 19 and 12, respectively) were collected at the hospital and kept frozen until just before use. They were analyzed using high-pH RP peptide fractionations/low-pH RP 2D nano-LC/ESI-MS/MS. Biomarker candidates were also investigated using Western blot analysis and sandwich ELISA on ND and/or sera. Results: We found distinct tendencies in protein expression and three candidate breast cancer biomarkers (carbonic anhydrase 2, catalase, and peroxiredoxin-2) whose levels differed significantly between ND specimens from patients with and without breast cancer. Conclusions and clinical relevance: These tendencies in protein expression and markers provide new ways to identify breast cancer patients. Therefore, RP/RP 2D LC/MS/MS analyses of ND and the above three markers are supported as a new breast cancer diagnostic technique.
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