Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer
- Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer
- 양원석; 문형곤; 김희성; 최의주; 유명희; 노동영; 이철주
- Journal of proteome research; drug resistance; quantitative proteomics; FKBP4; S100A9
- Issue Date
- Journal of proteome research
- VOL 11, NO 2, 1078-1088
- Although doxorubicin (Doxo) and docetaxel (Docet)
in combination are widely used in treatment regimens for a broad
spectrum of breast cancer patients, a major obstacle has emerged in
that some patients are intrinsically resistant to these chemotherapeutics.
Our study aimed to discover potential predictionmarkers of drug
resistance in needle-biopsied tissues of breast cancer patients prior to
neoadjuvant chemotherapy. Tissues collected before chemotherapy
were analyzed by mass spectrometry. A total of 2,331 proteins were
identified and comparatively quantified between drug sensitive (DS)
and drug resistant (DR) patient groups by spectral count. Of them,
298 proteins were differentially expressed bymore than 1.5-fold. Some
of the differentially expressed proteins (DEPs) were further confirmed
by Western blotting. Bioinformatic analysis revealed that the
DEPs were largely associated with drug metabolism, acute phase response signaling, and fatty acid elongation in mitochondria.
Clinical validation of two selected proteins by immunohistochemistry found that FKBP4 and S100A9 might be putative prediction
markers in discriminating the DR group from the DS group of breast cancer patients. The results demonstrate that a quantitative
proteomics/bioinformatics approach is useful for discovering prediction markers of drug resistance, and possibly for the
development of a new therapeutic strategy.
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