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Development of cancer biomarker heat shock protein 90α certified reference material using two different isotope dilution mass spectrometry techniques

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Abstract

Heat shock protein 90α (HSP90α) has been regarded as an important indicator for judging tumor metastasis and prognosis due to its significant upregulation in various tumors. Therefore, the accurate quantification of HSP90α is of great significance for clinical diagnosis and therapy of cancers. However, the lack of HSP90α certified reference material (CRM) leads to the accuracy and consistency of quantification methods not being effectively evaluated. Besides, quantitative results without traceability make comparisons between different studies difficult. In this study, an HSP90α solution CRM was developed from the recombinant protein raw material. The recombinant protein is a dimer, and the purity of the CRM candidate reached 96.71%. Both amino acid analysis-isotope dilution mass spectrometry (AAA-IDMS) and unique peptide analysis-isotope dilution mass spectrometry (UPA-IDMS) were performed to measure the content of HSP90α in the solution CRM candidate, and the certified value was assessed to be 66.2 ± 8.8 µg/g. Good homogeneity of the CRM was identified, and the stability examination suggested that the CRM was stable for at least 4 months at − 80 °C and for 7 days at 4 °C. With traceability to SI unit (kg), this CRM has potential to help establish a metrological traceability chain for quantification of HSP90α, which will make the quantification results standardized and comparable regardless of the quantitative methods.

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Funding

This work was funded by the National Key Research and Development Program of China (No.2022YFF0608401), National Natural Science Foundation of China (No.21927812), and Fundamental Research Funds of the National Institute of Metrology (AKYZD1907, AKYZD2111, AKYCX2211).

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Author notes

  1. Manman Zhu and Jingjing Li contributed equally to this work.

Authors and Affiliations

  1. Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing, 100029, People’s Republic of China

    Manman Zhu, Zhanying Chu, Lan Li, Bo Meng, Yang Zhao, Xiaoyun Gong, Ziyu Qu, Wei Mi, You Jiang, Liqing Wu, Xinhua Dai, Xiang Fang & Rui Zhai

  2. Beijing Institute of Metrology, Beijing, 100191, People’s Republic of China

    Jingjing Li

  3. College of Life Sciences, China Jiliang University, Hangzhou, 310018, People’s Republic of China

    Lan Li

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  1. Manman Zhu
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Zhu, M., Li, J., Chu, Z. et al. Development of cancer biomarker heat shock protein 90α certified reference material using two different isotope dilution mass spectrometry techniques. Anal Bioanal Chem 416, 913–923 (2024). https://doi.org/10.1007/s00216-023-05079-7

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  • DOI: https://doi.org/10.1007/s00216-023-05079-7

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