Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer

Won Suk Yang, Hyeong Gon Moon, Hee Sung Kim, Eui Ju Choi, Myeong Hee Yu, Dong Young Noh, Cheolju Lee

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 prediction markers 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 by more 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.

Original languageEnglish
Pages (from-to)1078-1088
Number of pages11
JournalJournal of Proteome Research
Volume11
Issue number2
DOIs
Publication statusPublished - 2012 Feb 3

Fingerprint

Chemotherapy
Proteomics
Breast Neoplasms
Drug Therapy
Pharmaceutical Preparations
docetaxel
Proteins
Computational Biology
Drug Resistance
Bioinformatics
Far-Western Blotting
Therapeutics
Acute-Phase Reaction
Tissue
Doxorubicin
Needles
Mitochondria
Mass Spectrometry
Fatty Acids
Immunohistochemistry

Keywords

  • drug resistance
  • FKBP4
  • neoadjuvant chemotherapy
  • quantitative proteomics
  • S100A9

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer. / Yang, Won Suk; Moon, Hyeong Gon; Kim, Hee Sung; Choi, Eui Ju; Yu, Myeong Hee; Noh, Dong Young; Lee, Cheolju.

In: Journal of Proteome Research, Vol. 11, No. 2, 03.02.2012, p. 1078-1088.

Research output: Contribution to journalArticle

Yang, Won Suk ; Moon, Hyeong Gon ; Kim, Hee Sung ; Choi, Eui Ju ; Yu, Myeong Hee ; Noh, Dong Young ; Lee, Cheolju. / Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer. In: Journal of Proteome Research. 2012 ; Vol. 11, No. 2. pp. 1078-1088.
@article{768c3e06ae054b1b95c40668237e9381,
title = "Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer",
abstract = "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 prediction markers 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 by more 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.",
keywords = "drug resistance, FKBP4, neoadjuvant chemotherapy, quantitative proteomics, S100A9",
author = "Yang, {Won Suk} and Moon, {Hyeong Gon} and Kim, {Hee Sung} and Choi, {Eui Ju} and Yu, {Myeong Hee} and Noh, {Dong Young} and Cheolju Lee",
year = "2012",
month = "2",
day = "3",
doi = "10.1021/pr2008187",
language = "English",
volume = "11",
pages = "1078--1088",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer

AU - Yang, Won Suk

AU - Moon, Hyeong Gon

AU - Kim, Hee Sung

AU - Choi, Eui Ju

AU - Yu, Myeong Hee

AU - Noh, Dong Young

AU - Lee, Cheolju

PY - 2012/2/3

Y1 - 2012/2/3

N2 - 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 prediction markers 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 by more 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.

AB - 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 prediction markers 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 by more 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.

KW - drug resistance

KW - FKBP4

KW - neoadjuvant chemotherapy

KW - quantitative proteomics

KW - S100A9

UR - http://www.scopus.com/inward/record.url?scp=84863080780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863080780&partnerID=8YFLogxK

U2 - 10.1021/pr2008187

DO - 10.1021/pr2008187

M3 - Article

C2 - 22074005

AN - SCOPUS:84863080780

VL - 11

SP - 1078

EP - 1088

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 2

ER -