Development and Validation of a Novel Plasma Protein Signature for Breast Cancer Diagnosis by Using Multiple Reaction Monitoring-based Mass Spectrometry.
OBJECTIVE
We aimed to develop a plasma protein signature for breast cancer diagnosis by using multiple reaction monitoring (MRM)-based mass spectrometry.


METHODS
Based on our previous studies, we selected 124 proteins for MRM. Plasma samples from 80 patients with breast cancer and 80 healthy women were used to develop a plasma proteomic signature by an MRM approach. The proteomic signature was then validated in plasma samples from 100 patients with breast cancer and 100 healthy women.


RESULTS
A total of 56 proteins were optimized for MRM. In the verification cohort, 11 proteins exhibited significantly differential expression in plasma from patients with breast cancer. Three proteins (neural cell adhesion molecule L1-like protein, apolipoprotein C-1 and carbonic anhydrase-1) with highest statistical significance which gave consistent results for patients of stage I and II breast cancer were selected and a 3-protein signature was developed using binary logistic regression analysis [area under the curve (AUC)=0.851, sensitivity=80.6%]. The 3-protein signature showed similar performance in an independent validation cohort with an AUC of 0.797 and sensitivity of 77.2% for detection of stage I and II breast cancer.


CONCLUSIONS
We developed a distinct plasma protein signature for breast cancer diagnosis based on an MRM-based approach, and the clinical value of the 3-protein signature was validated in an independent cohort.
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Han-Byoel
HB
Lee
R&D Center, Biomedieng Co. Ltd., Gyeonggi-do, Republic of Korea.
Un-Beom
UB
Kang
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hyeong-Gon
HG
Moon
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jiwoo
J
Lee
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kyung-Min
KM
Lee
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Minju
M
Yi
R&D Center, Biomedieng Co. Ltd., Gyeonggi-do, Republic of Korea.
Yong Sun
YS
Park
Department of Surgery, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea.
Jong Won
JW
Lee
Department of Surgery, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea.
Jong-Han
JH
Yu
Healthcare System Gangnam Center, Healthcare Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Seung Ho
SH
Choi
Healthcare System Gangnam Center, Healthcare Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Sang Heon
SH
Cho
Life Sciences Division, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Cheolju
C
Lee
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Wonshik
W
Han
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea dynoh@snu.ac.kr.
Dong-Young
DY
Noh
D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D006801:Humans; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D014408:Biomarkers, Tumor; D001798:Blood Proteins
Breast cancer; diagnosis; multiple reaction monitoring; plasma; proteomics