Breast cancer diagnosis by analysis of serum N-glycans using MALDI-TOF mass spectroscopy

Sae Byul Lee; Shambhunath Bose; Sei Hyun Ahn; Byung Ho Son; Beom Seok Ko; Hee Jeong Kim; Il Yong Chung; Jisun Kim; Woochang Lee; Myung-Su Ko; Kyungsoo Lee; Suhwan Chang; Hyoung Soon Park; Jong Won Lee; Dong-Chan Kim

doi:10.1371/journal.pone.0231004

Breast cancer diagnosis by analysis of serum N-glycans using MALDI-TOF mass spectroscopy

PLoS One. 2020 Apr 9;15(4):e0231004. doi: 10.1371/journal.pone.0231004. eCollection 2020.

Authors

Affiliations

¹ Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
² R&D Center, NOSQUEST Inc., Seongnam, Gyeonggi, Republic of Korea.
³ Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁴ Health Screening and Promotion Center, Asan Medical Center, Seoul, Republic of Korea.
⁵ Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁶ R&D Center, NOSVET Inc., Yongin, Gyeonggi, Republic of Korea.

Abstract

Blood and serum N-glycans can be used as markers for cancer diagnosis, as alterations in protein glycosylation are associated with cancer pathogenesis and progression. We aimed to develop a platform for breast cancer (BrC) diagnosis based on serum N-glycan profiles using MALDI-TOF mass spectroscopy. Serum N-glycans from BrC patients and healthy volunteers were evaluated using NosQuest's software "NosIDsys." BrC-associated "NosID" N-glycan biomarkers were selected based on abundance and NosIDsys analysis, and their diagnostic potential was determined using NosIDsys and receiver operating characteristic curves. Results showed an efficient pattern recognition of invasive ductal carcinoma patients, with very high diagnostic performance [area under the curve (AUC): 0.93 and 95% confidence interval (CI): 0.917-0.947]. We achieved effective stage-specific differentiation of BrC patients from healthy controls with 82.3% specificity, 84.1% sensitivity, and 82.8% accuracy for stage 1 BrC and recognized hormone receptor-2 and lymph node invasion subtypes based on N-glycan profiles. Our novel technique supplements conventional diagnostic strategies for BrC detection and can be developed as an independent platform for BrC screening.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / blood
Breast Neoplasms / blood
Breast Neoplasms / diagnosis*
Breast Neoplasms / pathology
Carcinoma, Ductal, Breast / blood
Carcinoma, Ductal, Breast / diagnosis
Case-Control Studies
Female
Glycosylation
Humans
Polysaccharides / blood*
ROC Curve
Sensitivity and Specificity
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

Biomarkers, Tumor
Polysaccharides

Grants and funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1149) The funder (Ministry of Health & Welfare) provided support in the form of salaries for the authors SBL, SHA, JWL but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NosQuest Inc. provided support in the form of salaries for authors SB, KL, DCK, and NosVet Inc. provided support in the form of salaries for authors HP but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.