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Study on the Relationship Between Differentially Expressed Proteins in Breast Cancer and Lymph Node Metastasis

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Abstract

Introduction

Lymph node metastasis is a cause of poor prognosis in breast cancer. Mass spectrometry-based proteomics aims to map the protein landscapes of biological samples and profile tumors more comprehensively. Here, proteomics was employed to identify differentially expressed proteins (DEPs) that were associated with lymph node metastasis.

Methods

Tandem mass tag (TMT) quantitative proteomic approaches were applied for extensive profiling of conditioned medium of MDA-MB-231 and MCF7 cell lines and serums of patients who did or did not have lymph node metastasis, and DEPs were analyzed by bioinformatics. Furthermore, potential secreted or membrane proteins MUC5AC, ITGB4, CTGF, EphA2, S100A4, PRDX2, and PRDX6 were selected for verification in 114 tissue microarray samples of breast cancer using the immunohistochemical method. The relevant data was analyzed and processed by independent sample t test, chi-square test, or Fisher’s exact test using SPSS 22.0 software.

Results

In the conditioned medium of MDA-MB-231 cell lines, 154 proteins were upregulated, while 136 were downregulated compared to those of MCF7. In the serum of patients with breast cancer and lymph node metastasis, 17 proteins were upregulated, and 5 proteins were downregulated compared to those without lymph node metastasis. Furthermore, according to tissue verification, CTGF, EphA2, S100A4, and PRDX2 were associated with breast cancer lymph node metastasis.

Conclusion

Our study provides a new perspective for the understanding of the role of DEPs (especially CTGF, EphA2, S100A4, and PRDX2) in the development and metastasis of breast cancer. They could become potential diagnostic and prognostic biomarkers and therapeutic targets.

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Acknowledgements

Thanks for the support from all fundings.

Funding

The study was funded by Medical Science and Technology Development Foundation, Nanjing Department of Health (YKK18083; ZKX20025). The Rapid Service Fee was funded by the authors.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

Yu-Lu Sun, Yi-Xin Zhao, Yi-Nan Guan, Xin You, Yin Zhang, Meng Zhang, Hong-Yan Wu, Wei-Jie Zhang and Yong-Zhong Yao contributed to the manuscript conception and design, statistical analysis, drafted previous versions of the manuscript, and read and approved the final manuscript.

Disclosures

Yu-Lu Sun, Yi-Xin Zhao, Yi-Nan Guan, Xin You, Yin Zhang, Meng Zhang, Hong-Yan Wu, Wei-Jie Zhang and Yong-Zhong Yao have nothing to disclose.

Compliance with Ethics Guidelines

This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of Nanjing Drum Tower Hospital (ethics committee approval number 2021-376). All participants signed informed consent to publish their data.

Data Availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Author information

Author notes

  1. Yu-Lu Sun and Yi-Xin Zhao contributed equally to this study.

Authors and Affiliations

  1. Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People’s Republic of China

    Yu-Lu Sun, Yi-Nan Guan, Xin You, Yin Zhang, Meng Zhang, Wei-Jie Zhang & Yong-Zhong Yao

  2. Medical School of Southeast University, Nanjing, Jiangsu Province, People’s Republic of China

    Yi-Xin Zhao

  3. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People’s Republic of China

    Hong-Yan Wu

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Sun, YL., Zhao, YX., Guan, YN. et al. Study on the Relationship Between Differentially Expressed Proteins in Breast Cancer and Lymph Node Metastasis. Adv Ther 40, 4004–4023 (2023). https://doi.org/10.1007/s12325-023-02588-w

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  • DOI: https://doi.org/10.1007/s12325-023-02588-w

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