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

• Published in: Experimental & molecular medicine Vol. 44; no. 1; pp. 36 - 44
• Main Authors: Suh, Eui Jin, Kabir, Mohammad Humayun, Kang, Un-Beom, Lee, Jong Won, Yu, Jonghan, Noh, Dong-Young, Lee, Cheolju
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2012; Springer Nature B.V; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Adult; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Early Detection of Cancer; Female; Gene Expression Profiling; Humans; Medical Biochemistry; Middle Aged; Molecular Medicine; Original; Pathology, Molecular - methods; Predictive Value of Tests; Prognosis; Proteomics; Stem Cells; Thrombospondin 1 - blood; Transcription Factors - blood; 생화학; biological markers; thrombospondin 1; mass spectrometry; proteomics; breast neoplasms; BRWD3 protein, human
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.3858/emm.2012.44.1.003

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.