Breast Cancer Diagnosis by Analysis of Serum N-glycans Using MALDI-TOF Mass Spectroscopy

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Apr 10

PMID 32271809

Citations 7

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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Glycosylation Alterations in Cancer Cells, Prognostic Value of Glycan Biomarkers and Their Potential as Novel Therapeutic Targets in Breast Cancer.

Peric L, Vukadin S, Petrovic A, Kuna L, Puseljic N, Sikora R Biomedicines. 2022; 10(12).

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Mass spectrometry in clinical glycomics: The path from biomarker identification to clinical implementation.

de Haan N, Wuhrer M, Ruhaak L Clin Mass Spectrom. 2021; 18:1-12.

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References

Haakensen V, Steinfeld I, Saldova R, Asadi Shehni A, Kifer I, Naume B . Serum N-glycan analysis in breast cancer patients--Relation to tumour biology and clinical outcome. Mol Oncol. 2015; 10(1):59-72. PMC: 5528923. DOI: 10.1016/j.molonc.2015.08.002. View

Li Q, Li G, Zhou Y, Zhang X, Sun M, Jiang H . Comprehensive N-Glycome Profiling of Cells and Tissues for Breast Cancer Diagnosis. J Proteome Res. 2019; 18(6):2559-2570. DOI: 10.1021/acs.jproteome.9b00073. View

Zhao H, Zou L, Geng X, Zheng S . Limitations of mammography in the diagnosis of breast diseases compared with ultrasonography: a single-center retrospective analysis of 274 cases. Eur J Med Res. 2015; 20:49. PMC: 4406115. DOI: 10.1186/s40001-015-0140-6. View

Gustafsson O, Briggs M, Condina M, Winderbaum L, Pelzing M, McColl S . MALDI imaging mass spectrometry of N-linked glycans on formalin-fixed paraffin-embedded murine kidney. Anal Bioanal Chem. 2014; 407(8):2127-39. PMC: 4357650. DOI: 10.1007/s00216-014-8293-7. View

Tyanova S, Cox J . Perseus: A Bioinformatics Platform for Integrative Analysis of Proteomics Data in Cancer Research. Methods Mol Biol. 2018; 1711:133-148. DOI: 10.1007/978-1-4939-7493-1_7. View

Handerson T, Camp R, Harigopal M, Rimm D, Pawelek J . Beta1,6-branched oligosaccharides are increased in lymph node metastases and predict poor outcome in breast carcinoma. Clin Cancer Res. 2005; 11(8):2969-73. DOI: 10.1158/1078-0432.CCR-04-2211. View

Zhang X, Wang Y, Qian Y, Wu X, Zhang Z, Liu X . Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics. PLoS One. 2014; 9(2):e87978. PMC: 3916363. DOI: 10.1371/journal.pone.0087978. View

King C, Kraus M, Aaronson S . Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985; 229(4717):974-6. DOI: 10.1126/science.2992089. View

Kim J, Park C, Um D, Baek K, Jo Y, An H . Mass spectrometric screening of ovarian cancer with serum glycans. Dis Markers. 2014; 2014:634289. PMC: 3932261. DOI: 10.1155/2014/634289. View

10.

Vagin O, Kraut J, Sachs G . Role of N-glycosylation in trafficking of apical membrane proteins in epithelia. Am J Physiol Renal Physiol. 2008; 296(3):F459-69. PMC: 2660186. DOI: 10.1152/ajprenal.90340.2008. View

11.

Chou C, Peng N, Chang T, Yang T, Hu C, Lin H . Clinical roles of breast 3T MRI, FDG PET/CT, and breast ultrasound for asymptomatic women with an abnormal screening mammogram. J Chin Med Assoc. 2015; 78(12):719-25. DOI: 10.1016/j.jcma.2015.06.018. View

12.

Schettini F, Buono G, Cardalesi C, Desideri I, De Placido S, Del Mastro L . Hormone Receptor/Human Epidermal Growth Factor Receptor 2-positive breast cancer: Where we are now and where we are going. Cancer Treat Rev. 2016; 46:20-6. DOI: 10.1016/j.ctrv.2016.03.012. View

13.

Taskin F, Polat Y, Erdogdu I, Turkdogan F, Ozturk V, Ozbas S . Problem-solving breast MRI: useful or a source of new problems?. Diagn Interv Radiol. 2018; 24(5):255-261. PMC: 6135053. DOI: 10.5152/dir.2018.17504. View

14.

Ashkani J, Naidoo K . Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes. Sci Rep. 2016; 6:26451. PMC: 4873817. DOI: 10.1038/srep26451. View

15.

Hu M, Lan Y, Lu A, Ma X, Zhang L . Glycan-based biomarkers for diagnosis of cancers and other diseases: Past, present, and future. Prog Mol Biol Transl Sci. 2019; 162:1-24. DOI: 10.1016/bs.pmbts.2018.12.002. View

16.

Gebrehiwot A, Melka D, Kassaye Y, Gemechu T, Lako W, Hinou H . Exploring serum and immunoglobulin G N-glycome as diagnostic biomarkers for early detection of breast cancer in Ethiopian women. BMC Cancer. 2019; 19(1):588. PMC: 6580580. DOI: 10.1186/s12885-019-5817-8. View

17.

Lee T . Comparison of Breast Cancer Screening Results in Korean Middle-Aged Women: A Hospital-based Prospective Cohort Study. Osong Public Health Res Perspect. 2013; 4(4):197-202. PMC: 3767103. DOI: 10.1016/j.phrp.2013.06.002. View

18.

Blows F, Driver K, Schmidt M, Broeks A, van Leeuwen F, Wesseling J . Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010; 7(5):e1000279. PMC: 2876119. DOI: 10.1371/journal.pmed.1000279. View

19.

De Leoz M, Young L, An H, Kronewitter S, Kim J, Miyamoto S . High-mannose glycans are elevated during breast cancer progression. Mol Cell Proteomics. 2010; 10(1):M110.002717. PMC: 3013453. DOI: 10.1074/mcp.M110.002717. View

20.

Park C, Jo Y, Jo E . Enhancement of ovarian tumor classification by improved reproducibility in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of serum glycans. Anal Biochem. 2013; 443(1):58-65. DOI: 10.1016/j.ab.2013.07.048. View