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Detection and identification of potential biomarkers of breast cancer

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Abstract

Purpose

Noninvasive and convenient biomarkers for early diagnosis of breast cancer remain an urgent need. The aim of this study was to discover and identify potential protein biomarkers specific for breast cancer.

Methods

Two hundred and eighty-two (282) serum samples with 124 breast cancer and 158 controls were randomly divided into a training set and a blind-testing set. Serum proteomic profiles were analyzed using SELDI-TOF-MS. Candidate biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays and western blot technique.

Results

A total of 3 peaks (m/z with 6,630, 8,139 and 8,942 Da) were screened out by support vector machine to construct the classification model with high discriminatory power in the training set. The sensitivity and specificity of the model were 96.45 and 94.87%, respectively, in the blind-testing set. The candidate biomarker with m/z of 6,630 Da was found to be down-regulated in breast cancer patients, and was identified as apolipoprotein C-I. Another two candidate biomarkers (8,139, 8,942 Da) were found up-regulated in breast cancer and identified as C-terminal-truncated form of C3a and complement component C3a, respectively. In addition, the level of apolipoprotein C-I progressively decreased with the clinical stages I, II, III and IV, and the expression of C-terminal-truncated form of C3a and complement component C3a gradually increased in higher stages.

Conclusions

We have identified a set of biomarkers that could discriminate breast cancer from non-cancer controls. An efficient strategy, including SELDI-TOF-MS analysis, HPLC purification, MALDI-TOF-MS trace and LC-MS/MS identification, has been proved very successful.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (30772273). All authors wish to thank Dr. Liwei Mi and Dr. Shutang Wen for the preparation of this manuscript.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, Henan, People’s Republic of China

    Yuxia Fan, Jiachen Wang, Qiuliang Liu, Yingzhong Fan, Mengquan Li & Jiaxiang Wang

  2. Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, People’s Republic of China

    Yang Yang

  3. Institute of Cancer, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, People’s Republic of China

    Jiekai Yu & Shu Zheng

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  1. Yuxia Fan
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  2. Jiachen Wang
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  3. Yang Yang
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  4. Qiuliang Liu
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  5. Yingzhong Fan
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  7. Shu Zheng
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  8. Mengquan Li
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  9. Jiaxiang Wang
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Correspondence to Jiaxiang Wang.

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Fan, Y., Wang, J., Yang, Y. et al. Detection and identification of potential biomarkers of breast cancer. J Cancer Res Clin Oncol 136, 1243–1254 (2010). https://doi.org/10.1007/s00432-010-0775-1

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  • DOI: https://doi.org/10.1007/s00432-010-0775-1

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