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A Panel of Regulated Proteins in Serum from Patients with Cervical Intraepithelial Neoplasia and Cervical Cancer

Boichenko, A. P., Govorukhina, N., Klip, H. G., van der Zee, A. G. J., Guezel, C., Luider, T. M. & Bischoff, R., Nov-2014, In : Journal of Proteome Research. 13, 11, p. 4995-5007 13 p.

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  • A Panel of Regulated Proteins in Serum from Patients with Cervical

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DOI

We developed a discoveryvalidation mass-spectrometry-based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using iTRAQ, label-free shotgun, and targeted mass-spectrometric quantification. In the discovery stage we used a pooling strategy for the comparative analysis of immunodepleted serum and revealed 15 up- and 26 down-regulated proteins in patients with early- (CES) and late-stage (CLS) cervical cancer. The analysis of nondepleted serum samples from patients with CIN, CES, an CLS and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein, and vitamin D-binding protein. We validated our findings using a fast UHPLC/MRM method in an independent set of serum samples from patients with cervical cancer or CIN and healthy controls as well as serum samples from patients with ovarian cancer (more than 400 samples in total). The panel of six proteins showed 67% sensitivity and 88% specificity for discrimination of patients with CIN from healthy controls, a stage of the disease where current protein-based biomarkers, for example, squamous cell carcinoma antigen (SCCA), fail to show any discrimination. Additionally, combining the six-protein panel with SCCA improves the discrimination of patients with CES and CLS from healthy controls.

Original languageEnglish
Pages (from-to)4995-5007
Number of pages13
JournalJournal of Proteome Research
Volume13
Issue number11
Publication statusPublished - Nov-2014

    Keywords

  • cervical cancer, cervical intraepithelial neoplasia, protein panel, LC-MS/MS, alpha-1-antitrypsin, alpha-1-acid-glycoprotein, haptoglobin, serotransferrin, vitamin D-bidning protein, alpha-2-HS-glycoprotein, SQUAMOUS-CELL CARCINOMA, HIGH-ABUNDANCE PROTEINS, MASS-SPECTROMETRY, PLASMA PROTEOME, TUMOR-MARKERS, SAMPLE PREPARATION, STATISTICAL-MODEL, DATABASE SEARCH, ANTIGEN, HAPTOGLOBIN

ID: 14740601