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Comprehensive lipid profiling of plasma in patients with benign breast tumor and breast cancer reveals novel biomarkers

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Abstract

Abnormal lipid metabolism is a common feature in most solid tumors, and occurs in early stages of the tumor progression. As benign breast tumor is different from malignant tumor of breast cancer, it is particularly important to take benign breast tumor into consideration when investigating cancer biomarkers. In this study, by using a normal-phase/reversed-phase two-dimensional liquid chromatography-mass spectrometry (NP/RP 2D LC-MS) method, we conducted comprehensive lipid profiling in human plasma obtained from six benign breast tumor patients and five breast cancer patients, as well as nine healthy controls. As a result, 512 lipid species were successfully identified. Principal component analysis allowed clear separation of the three groups. Quantitative analysis revealed that many lipid contents were similar in benign and malignant breast tumors compared with controls, and these were proposed as potential breast tumor biomarkers other than breast cancer biomarkers. Two phosphatidylinositol (PI) species, including PI (16:0/16:1) and PI (18:0/20:4), could differentiate between benign and malignant breast tumors, as well as breast cancer patients and healthy controls, indicating that they could be utilized as potential breast cancer biomarkers. In addition, PI (16:0/18:1), phosphatidylglycerol (36:3), and glucosylceramide (d18:1/15:1) were demonstrated to be potential biomarkers to evaluate the level of malignancy of breast tumor. Taken together, our results indicate the usefulness of lipid profiling in the discrimination between patients with breast cancer and non-carcinoma lesions, which might provide assistance in clinical diagnosis.

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Abbreviations

BPCs:

Base peak chromatograms

CEF:

Compound exchange format

Cer:

Ceramide

DG:

Diacylglycerol

EICs:

Extracted ion chromatograms

FFA:

Free fatty acid

GalCer:

Galactosylceramide

GCS:

Glucosylceramide synthase

GluCer:

Glucosylceramide

LacCer:

Lactosylceramide

LPC:

Lysophosphatidylcholine

LPE:

Lysophosphatidylethanolamine

LPG:

Lysophosphatidylglycerol

MG:

Monoacylglycerol

MS/MS:

Tandem mass spectrometry

NP/RP 2D LC-MS:

Normal-phase/reversed-phase two-dimensional lipid chromatography-mass spectrometry

PC:

Phosphatidylcholine

PCA:

Principal component analysis

PE:

Phosphatidylethanolamine

PG:

Phosphatidylglycerol

PI:

Phosphatidylinositol

PI3K:

Phosphatidylinositol 3-kinase

PIP3:

Phosphatidylinositol-3,4,5-tris-phosphate

PKC:

Protein kinase C

PS:

Phosphatidylserine

PTEN:

Phosphatase and tensin homologue deleted on chromosome 10

QToF:

Quadrupole Time-of-Flight

SCD1:

Stearoyl-CoA desaturase

SM:

Sphingomyelin

TG:

Triacylglycerol

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Acknowledgment

This study was financially supported by the National Natural Science Foundation of China (grant no. 21175005).

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    Authors and Affiliations

    1. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China

      Li Yang, Xinge Cui, Min Li, Yu Bai & Huwei Liu

    2. Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, Beijing, 100730, China

      Xinge Cui

    3. Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China

      Ningning Zhang, Xiaohong Han & Yuankai Shi

    4. Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China

      Ningning Zhang, Xiaohong Han & Yuankai Shi

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    1. Li Yang
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    Correspondence to Yuankai Shi or Huwei Liu.

    Additional information

    Published in the topical collection Lipidomics with guest editor Michal Holčapek.

    Li Yang and Xinge Cui contributed equally to this work.

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    Yang, L., Cui, X., Zhang, N. et al. Comprehensive lipid profiling of plasma in patients with benign breast tumor and breast cancer reveals novel biomarkers. Anal Bioanal Chem 407, 5065–5077 (2015). https://doi.org/10.1007/s00216-015-8484-x

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