4.7 Article

Comprehensive N-Glycome Profiling of Cells and Tissues for Breast Cancer Diagnosis

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 18, Issue 6, Pages 2559-2570

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.9b00073

Keywords

breast cancer; benign breast tumor; N-glycans; PGC-ESI-MS/MS profiling

Funding

  1. National Natural Science Foundation of China [31600646]
  2. Natural Science Foundation of Shandong Province [ZR2016HB42]
  3. Fundamental Research Funds for the Central Universities [201762002]
  4. China Postdoctoral Science Foundation [2017M612356]
  5. Qingdao Basic and Applied Research Project [18-2-2-25-jch]
  6. National Science and Technology Major Project for Significant New Drugs Development [2018ZX09735004]
  7. NSFC-Shandong Joint Fund for Marine Science Research Centers [U1606403]
  8. Taishan scholar project special funds [TS201511011]

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Aberrant protein glycosylation is observed in the progression of many types of diseases, including different cancers. In this study, we assess differential N-glycan patterns of human breast cancer cells and tissues by PGC-ESI-MS/MS. Compared with mammary epithelial cells, high-mannose glycans were significantly elevated in breast cancer cells. However, the alteration of N-glycans in tissues was more obvious than that in cells. Sixty-three kinds of different N-glycans were stably identified, and 38 types of them exhibited significant differences between paracarcinoma and breast cancer tissues. High-mannose glycans and core-fucosylated glycans were increased in the breast cancer tissues, while bisected glycans and sialylated glycans were decreased. Moreover, a total of 27 types of N-glycans displayed evident differences between benign breast tumor and breast cancer tissues, and most of them including bisected and sialylated glycans exhibited decreased relative abundances in cancer tissues. Overall, three high-mannose N-glycans (F0H6N2S0, F0H7N2S0, F0H8N2S0) exhibited significant diagnostic accuracy in both breast cancer cells and tissues, suggesting their potential role in biomarkers. Furthermore, a negative correlation between sialylated glycans and age of patients was identified. In conclusion, our results may be beneficial to understand the role that N-glycan plays on the progression of breast cancer and propose potential diagnostic biomarkers.

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