Potential plasma biomarkers of bladder cancer identified by proteomic analysis: A pilot study

Abstract

Background. Bladder cancer diagnosis and surveillance includes cystoscopy and cytology. New methods for the detection of bladder cancer are needed, because cystoscopy is invasive and expensive, and because urine cytology is not sensitive enough. Objectives. The aim of the study was to select potential plasma protein markers for bladder cancer which could be useful in developing a specific laboratory test to improve diagnosis and to establish treatment strategies in order to prevent the recurrence of the disease. Material and methods. Plasma proteome maps were prepared based on 2-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), combined with image gel analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of plasma samples from patients with urothelial bladder cancer, and they were compared to normal samples. Results. The analyses of bladder cancer plasma samples allowed us to distinguish 3 groups of proteins whose relative abundance differed from that in normal samples. The 1 st one comprised modified forms of plasma transferrin, fibrinogen gamma and complement C3b, which were absent in normal plasma. The 2 nd group comprised haptoglobin, alpha-2-macroglobulin, vitamin D-binding protein, and pigment epithelium-derived factor, which occurred in the cancerous samples in large quantities. The 3 rd group consisted of 3 molecular forms of immunoglobulin M (IgM), the relative abundance of which was significantly lower in the cancerous plasma samples. Conclusions. The data indicated potential plasma biomarkers associated with inflammation, immunity and coagulation processes accompanying bladder cancer. They could be used for the development of a laboratory test(s) useful in clinical practice.

Circulating proteomic signature for detection of biomarkers in bladder cancer patients

“…Three forms of haptoglobin have been identified which may indicate numerous potential splices variants and post-translational modification of haptoglobin. Our finding is consistent with previous ones reporting elevated haptoglobin levels in Turkish and Polish bladder cancer patients 17,31 www.nature.com/scientificreports/ Under normal physiological conditions Haptoglobin stabilize hemoglobin (Hb) through binding and forming a complex with it. Haptoglobin has also significant protective properties against oxidative damage by Hb 32 .…”

“…Two dimensional gel-electrophoresis (2D-E) combined with mass spectrometry (MS) have evolved greatly and are capable of analyzing and identifying multiple differentially expressed proteins with high sensitivity and specificity 13,14 . Recent years have witnessed tremendous expansion in circulating biomarkers analysis by liquid chromatography/MS to develop bladder cancer biomarkers for diagnosis and/ or prognosis [15][16][17] . In this context several single biomarker molecules, with mechanistic relevance to bladder cancer, have been identified including complement C3b, CYFRA 21-1, ApoA4, ApoE and soluble E-cadherin [17][18][19] .…”

“…Recent years have witnessed tremendous expansion in circulating biomarkers analysis by liquid chromatography/MS to develop bladder cancer biomarkers for diagnosis and/ or prognosis [15][16][17] . In this context several single biomarker molecules, with mechanistic relevance to bladder cancer, have been identified including complement C3b, CYFRA 21-1, ApoA4, ApoE and soluble E-cadherin [17][18][19] . Also, extensive research has been performed on multi-markers model which has led to the identification of panels of biomarkers that are differentially regulated in bladder carcinoma 20,21 .…”

Proteomic profiling of bladder cancer for precision medicine in the clinical setting: A review for the busy urologist

“…Lemańska-Perek et al [ 90 ] analyzed BC plasma samples and found three groups of proteins with different expression levels compared with normal samples. The first group were proteins that should not exist in normal plasma, including fibrinogen γ, plasma transferrin, and C3b.…”

“…Proteomics markers identified in different human samples are summarized in Table 4 [ 53 55 57 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 ].…”