Exp Mol Med.  2012 Jan;44(1):36-44. 10.3858/emm.2012.44.1.003.

Comparative profiling of plasma proteome from breast cancer patients reveals thrombospondin-1 and BRWD3 as serological biomarkers

Affiliations
  • 1BRI, Korea Institute of Science and Technology, Seoul 136-130, Korea. clee270@kist.re.kr
  • 2University of Science and Technology, Daejeon 305-350, Korea.
  • 3Biomedieng Co. Ltd., Seongnam 462-121, Korea.
  • 4Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-042, Korea.
  • 5Cancer Research Institute, Seoul National University, College of Medicine, Seoul 110-799, Korea.

Abstract

Breast cancer is the most common cancer in women worldwide. It is necessary to identify biomarkers for early detection, to make accurate prognoses, and to monitor for any recurrence of the cancer. In order to identify potential breast cancer biomarkers, we analyzed the plasma samples of women diagnosed with breast cancer and age-matched normal healthy women by mTRAQ-based stable isotope-labeling mass spectrometry. We identified and quantified 204 proteins including thrombospondin-1 (THBS1) and bromodomain and WD repeat-containing protein 3 (BRWD3) which were increased by more than 5-fold in breast cancer plasma. The plasma levels of the two proteins were evaluated by Western blot assay to confirm for their diagnostic value as serum markers. A 1.8-fold increase in BRWD3 was observed while comparing the plasma levels of breast cancer patients (n = 54) with age-matched normal healthy controls (n = 30), and the area under the receiver operating characteristic curve (AUC) was 0.917. THBS1 was detected in pooled breast cancer plasma at the ratio similar to mTRAQ ratio (> 5-fold). The AUC value for THBS1 was 0.875. The increase of THBS1 was more prominent in estrogen receptor negative and progesterone receptor negative patients than receptor-positive patients. Our results are evidence of the diagnostic value of THBS1 in detecting breast cancer. Based on our findings, we suggest a proteomic method for protein identification and quantification lead to effective biomarker discovery.

Keyword

biological markers; breast neoplasms; BRWD3 protein, human; mass spectrometry; proteomics; thrombospondin 1

MeSH Terms

Adult
Breast Neoplasms/*diagnosis/genetics/pathology
Early Detection of Cancer
Female
Gene Expression Profiling
Humans
Middle Aged
Pathology, Molecular/methods
Predictive Value of Tests
Prognosis
*Proteomics
Thrombospondin 1/*blood
Transcription Factors/*blood
Tumor Markers, Biological/*blood
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