Quantitative assessment of human serum transferrin receptor in breast cancer patients pre- and post-chemotherapy using peptide immunoaffinity enrichment coupled with targeted proteomics

作者: Qingqing Xu , Mingchen Zhu , Ting Yang , Feifei Xu , Yuan Liu

DOI: 10.1016/J.CCA.2015.05.022

关键词: Breast cancerPeptideLiquid chromatography–mass spectrometryBone marrow failureProteomicsTransferrin receptorTandem mass spectrometryPharmacologyChemotherapyMedicineMolecular biologyClinical biochemistryBiochemistryBiochemistry, medicalGeneral Medicine

摘要: Abstract Background sTfR, a soluble form of transferrin receptor in serum, has been suggested as an indicator bone marrow failure breast cancer patients receiving chemotherapy. However, intensive chemotherapy could also cause reduction sTfR to level below the LOQ most assays. Methods An advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS)–based targeted proteomics assay coupled with peptide immunoaffinity enrichment (SISCAPA) was developed and validated for monitoring sTfR. Results Tryptic 681VEYHFLSPYVSPK693 selected surrogate analyte quantification. High-abundant proteins were first removed from followed by SISCAPA that effective sensitivity enhancement. The resulting can achieve 100 ng/ml (~ 10-fold increase). Then, levels pre- post-chemotherapy, healthy volunteers accurately quantified 1.77 ± 0.53 μg/ml, 0.98 ± 0.26 μg/ml 1.66 ± 0.50 μg/ml, respectively, using standard addition method. While there no evidence difference between volunteers, differential post-chemotherapy obtained. Comparison SISCAPA-targeted ELISA indicated former approach provided lower value Conclusions may allow quantification low-abundant more accurate manner.

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