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Portable detection of serum HER-2 in breast cancer by a pressure-based platform

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Abstract

A high serum HER-2 extracellular domain (sHER-2 ECD) level has a reverse association with tumor behaviors. In this study, a portable platform for the disease biomarker sHER-2 ECD detection has been established using a pressure-based bioassay. The pressure bioassay consists of a monoclonal antibody immobilized on an eight-well strip, the analyte HER-2, and another monoclonal antibody labeled with the Pt nanoparticles (PtNPs), which have the catalytic ability to decompose H2O2 into H2O and O2(g). The increased pressure due to O2(g) generation is measured by a hand-held pressure meter. A total of 34 serum samples were collected to validate the performance of the pressure bioassay. The results showed that the pressure bioassay platform of HER-2 had a dynamic range from 2 to 50 ng/mL with a limit of detection (LOD) of 2 ng/mL, which was consistent with the ELISA result. In the real serum samples, there was a significant correlation between sHER-2 ECD level and several clinicopathological parameters, especially tissue HER-2 status. Furthermore, the sHER-2 ECD level was found to decrease after targeted therapy in a patient with tHER-2 positive. Overall, this bioassay can facilitate breast cancer diagnosis and prognosis in clinical scenarios and resource-limited areas.

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Abbreviations

CLIA:

Chemiluminescence immunoassay

CRP:

C-reactive protein

ELISA:

Enzyme-linked immunosorbent assay

ER:

Estrogen receptor

FDA:

US Food and Drug Administration

HER-2:

Human epidermal growth factor receptor type 2

MMP-9:

Matrix metalloprotein-9

OS:

Overall survival

PASS:

Pressure-based bioassay

POCT:

Point-of-care testing

PR:

Progesterone receptor

PtNPs:

Pt nanoparticles

sHER-2 ECD:

Serum HER-2 extracellular domain

tHER-2:

Tissue HER-2

References

  1. Ménard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003;22(42):6570–8.

    Article  Google Scholar 

  2. Sorensen PD, Jakobsen EH, Langkjer ST, Bokmand S, Ostergaard B, Olsen DA, et al. Serum HER-2 concentrations for monitoring women with breast cancer in a routine oncology setting. Clin Chem Lab Med. 2009;47(9):1117–23.

    Article  Google Scholar 

  3. Muller V, Witzel I, Luck HJ, et al. Prognostic and predictive impact of the HER-2/neu extracellular domain (ECD) in the serum of patients treated with chemotherapy for metastatic breast cancer. Breast Cancer Res Treat. 2004;86:1.

    Article  Google Scholar 

  4. Isola JJ, Holli K, Oksa H, Teramoto Y, Kallioniemi OP. Elevated erbB-2 oncoprotein levels in preoperative and follow-up serum samples define an aggressive disease course in patients with breast cancer. Cancer. 1994;73(3):652–8.

    Article  CAS  Google Scholar 

  5. Willsher PC, Beaver J, Pinder S, Bell JA, Ellis IO, Blamey RW, et al. Prognostic significance of serum c-erbB-2 protein in breast cancer patients. Breast Cancer Res Treat. 1996;40(3):251–5.

    Article  CAS  Google Scholar 

  6. Schwartz MK, Smith C, Schwartz DC, Dnistrian A, Neiman I. Monitoring therapy by serum HER-2/neu. Int J Biol Markers. 2000;15(4):324–9.

    Article  CAS  Google Scholar 

  7. Carney WP, Neumann R, Lipton A, Leitzel K, Ali S, Price CP. Monitoring the circulating levels of the HER2/neu oncoprotein in breast cancer. Clin Breast Cancer. 2004;5(2):105–16.

    Article  CAS  Google Scholar 

  8. Hayashi N, Nakamura S, Tokuda Y, Yagata H, Yoshida A, Ota H, et al. Serum HER2 levels determined by two methods in patients with metastatic breast cancer. Int J Clin Oncol. 2011;17(1):55–62.

    Article  Google Scholar 

  9. Lebedeva I, Tan L-D, Xu Y-Y, Yu Y, Li X-Q, Chen Y, et al. Serum HER2 level measured by dot blot: a valid and inexpensive assay for monitoring breast cancer progression. PLoS One. 2011;6(4):e18764.

    Article  Google Scholar 

  10. Zhu Z, Guan Z, Liu D, Jia S, Li J, Lei Z, et al. Translating molecular recognition into a pressure signal to enable rapid, sensitive, and portable biomedical analysis. Angew Chem Int Ed Engl. 2015;54(36):10448–53.

    Article  CAS  Google Scholar 

  11. Ji T, Liu D, Liu F, Li J, Ruan Q, Song Y, et al. A pressure-based bioassay for the rapid, portable and quantitative detection of C-reactive protein. Chem Commun (Camb). 2016;52(54):8452–4.

    Article  CAS  Google Scholar 

  12. Hamasaki T, Kashiwagi T, Imada T, Nakamichi N, Aramaki S, Toh K, et al. Kinetic analysis of superoxide anion radical-scavenging and hydroxyl radical-scavenging activities of platinum nanoparticles. Langmuir. 2008;24(14):7354–64.

    Article  CAS  Google Scholar 

  13. Song Y, Wang Y, Qin L. A multistage volumetric bar chart chip for visualized quantification of DNA. J Am Chem Soc. 2013;135(45):16785–8.

    Article  CAS  Google Scholar 

  14. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  Google Scholar 

  15. Reix N, Malina C, Chenard MP, Bellocq JP, Delpous S, Moliere S, et al. A prospective study to assess the clinical utility of serum HER2 extracellular domain in breast cancer with HER2 overexpression. Breast Cancer Res Treat. 2016;160(2):249–59.

    Article  CAS  Google Scholar 

  16. Shukla S, Singh BK, Pathania OP, Jain M. Evaluation of HER2/neu oncoprotein in serum & tissue samples of women with breast cancer. Indian J Med Res. 2016;143(Supplement):S52–S8.

    Article  Google Scholar 

  17. Esteva FJ, Cheli CD, Fritsche H, Fornier M, Slamon D, Thiel RP, et al. Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies. Breast Cancer Res. 2005;7(4):R436–43.

    Article  CAS  Google Scholar 

  18. Fornier MN, Seidman AD, Schwartz MK, Ghani F, Thiel R, Norton L, et al. Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate. Ann Oncol. 2005;16(2):234–9.

    Article  CAS  Google Scholar 

  19. Lee SB, Lee JW, Yu JH, et al. Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer. BMC Cancer. 2014;14:929.

    Article  Google Scholar 

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Funding

This work was supported by the Major Scientific Research Program of PLA, China (No. AWS17J009) and National Natural Science Foundation of P.R. China (No. 81101904).

Author information

Author notes

  1. Qian Tao, Xinyi Wu and Qingyuan Lin contributed equally to this work.

Authors and Affiliations

  1. Chinese People’s Liberation Army No. 174 Clinical College, Anhui Medical University, Xiamen, 361000, China

    Qian Tao, Haiyan Zheng & Tianhai Ji

  2. Department of Pathology, Affiliated Chenggong Hospital, Xiamen University, Xiamen, 361000, Fujian, China

    Qian Tao, Qingyuan Lin, Haiyan Zheng, Wensheng Yang & Tianhai Ji

  3. Department of Pathology, Xiang’an Hospital of Xiamen University, Xiamen, 361000, Fujian, China

    Qian Tao

  4. Department of Breast Surgery, Affiliated No. 1 Hospital, Xiamen University, Xiamen, 361000, Fujian, China

    Xinyi Wu

  5. Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen, 361021, Fujian, China

    Dan Liu

  6. Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, Fujian, China

    Chaoyong James Yang

Authors
  1. Qian Tao
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  2. Xinyi Wu
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  3. Qingyuan Lin
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  4. Haiyan Zheng
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  5. Wensheng Yang
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  6. Dan Liu
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  7. Chaoyong James Yang
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  8. Tianhai Ji
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Corresponding authors

Correspondence to Dan Liu or Tianhai Ji.

Ethics declarations

The authors declare that all individual participants from whom the serum samples were obtained gave informed consent, and the studies have been approved by the Affiliated Chenggong Hospital, Xiamen University Ethics Committee and have been performed in accordance with ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

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Tao, Q., Wu, X., Lin, Q. et al. Portable detection of serum HER-2 in breast cancer by a pressure-based platform. Anal Bioanal Chem 410, 7489–7498 (2018). https://doi.org/10.1007/s00216-018-1364-4

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  • DOI: https://doi.org/10.1007/s00216-018-1364-4

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