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Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer

Authors

  • Mårten Lindén,

    1. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
    2. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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  • Sara Bergström Lind,

    Corresponding author
    1. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
    • Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden Fax: +46-18-471-4808
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  • Corina Mayrhofer,

    1. Division of Molecular Biometry, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
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  • Ulrika Segersten,

    1. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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  • Kenneth Wester,

    1. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
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  • Yaroslav Lyutvinskiy,

    1. Division of Molecular Biometry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
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  • Roman Zubarev,

    1. Division of Molecular Biometry, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
    2. Division of Molecular Biometry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
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  • Per-Uno Malmström,

    1. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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  • Ulf Pettersson

    1. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
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    • These authors have shared senior authorship.


Abstract

Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (p<0.05) in bladder cancer samples compared with control urine samples. The increased abundance found in urine from bladder cancer patients compared with controls was confirmed with Western blot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66–85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.

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