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Gangliosides profiling in serum of breast cancer patient: GM3 as a potential diagnostic biomarker

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Abstract

Gangliosides altered during the pathological conditions and particularly in cancers. Here, we aimed to profile the gangliosides in breast cancer serum and propose potential biomarkers. LC-FTMS method was first used to identify all the ganglioside species in serum, then LC-MS/MS-MRM method was employed to quantitate the levels of gangliosides in serum from healthy volunteers and patients with benign breast tumor or breast cancer. 49 ganglioside species were determined, including GM1, GM2, GM3, GD1, GD3 and GT1 species. Compared to healthy volunteers, the levels of GM1, GM2, GM3, GD1 and GD3 displayed a rising trend in breast cancer patients. In particular, as the major glycosphingolipid component, GM3 showed excellent diagnostic accuracy in cancer serum (AUC > 0.9). PCA profile of the GM3 species showed clear distinction between normal and cancer serum. What’s more, ROC curve proved great diagnostic accuracy of GM3 between cancer and benign serum. In addition, GM3 was discovered as a diagnostic marker to differentiate luminal B subtype from other subtypes. Furthermore, a positive correlation between GM3 and Ki-67 status of patients was identified. In conclusion, our results introduced the alteration patterns of serum gangliosides in breast cancer and suggested serum GM3 as a potential diagnostic biomarker in breast cancer diagnosis and luminal B subtype distinction.

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Abbreviations

LA:

Luminal A subtype

LB:

Luminal B subtype

HER:

HER-2 overexpressing subtype

BS:

Basal-like subtype

Normal:

Healthy volunteers

Benign:

Benign breast tumor patients

Cancer:

Breast cancer patients

ROC:

Receiver operator characteristics

PCA:

Principal component analysis

MRM:

Multiple reaction monitoring

LC-FTMS:

Liquid chromatography-Fourier transform mass spectrometry.

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Acknowledgments

This work was supported by Grants from National Natural Science Foundation of China (31600646), Natural Science Foundation of Shandong Province (ZR2016HB42), the Fundamental Research Funds for the Central Universities (201762002), Qingdao Basic and Applied Research Project (18-2-2-25-jch), National Science and Technology Major Project for Significant New Drugs Development (2018ZX09735004), NSFC-Shandong Joint Fund for Marine Science Research Centers (U1606403) and Taishan scholar project special funds (TS201511011).

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Authors and Affiliations

  1. Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, China

    Qinying Li, Qianyun Fu, Hao Jiang, Guangli Yu & Guoyun Li

  2. Qingdao Municipal Hospital, The Affiliated Qingdao Municipal Hospital, Qingdao University Medical College, Qingdao, 266071, China

    Mei Sun & Mingsheng Yu

  3. Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266003, China

    Hao Jiang, Guangli Yu & Guoyun Li

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  1. Qinying Li
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Correspondence to Guoyun Li.

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Li, Q., Sun, M., Yu, M. et al. Gangliosides profiling in serum of breast cancer patient: GM3 as a potential diagnostic biomarker. Glycoconj J 36, 419–428 (2019). https://doi.org/10.1007/s10719-019-09885-z

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