Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures

Ferrari, Emanuele; Wittig, Andrea; Basilico, Fabrizio; Rossi, Rossana; Palma, Antonella De; Silvestre, Dario Di; Sauerwein, W.; Mauri, Pierluigi

doi:10.3390/molecules24040794

Cited by 30 publications

(29 citation statements)

References 60 publications

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“…It has been suggested to play a role in stabilization of extracellular matrix by binding to hyaluronic acid, may be involved in modulating inflammation and inhibit apoptosis. Previous studies have identified ITIH4 as a potential diagnostic and prognostic marker for a number of diseases that include acute ischemic stroke, ovarian cancer, interstitial cystitis, liver fibrosis [ 23 ] and its increased levels were seen in cases of thyroid cancer [ 24 ]. The decrease in the abundance of ITIH4 in our study was confirmed by immunoblotting.…”

Section: Discussionmentioning

confidence: 99%

Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment

2020

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Thyroid hormones critically modulate body homeostasis and haemostasis by regulating energy and metabolism. Previous studies have focused on individual pathways or proteins that are affected by increases in thyroid hormone levels, while an overall plasma proteomic signature of this increased level is lacking. Herein, an integrated untargeted proteomic approach with network analysis was used to identify changes in circulating proteins in the plasma proteome between hyperthyroid and euthyroid states. Plasma from 10 age-matched subjects at baseline (hyperthyroid) and post treatment with carbimazole (euthyroid) was compared by difference gel electrophoresis (DIGE) and matrix-assisted laser desorption/ionization time of flight (MALDI TOF) mass spectrometry (MS). A total of 20 proteins were identified with significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two states (12 increased and 8 decreased in abundance in the hyperthyroid state). Twelve protein spots corresponding to ten unique proteins were significantly more abundant in the hyperthyroid state compared with the euthyroid state. These increased proteins were haptoglobin (HP), hemopexin (HPX), clusterin (CLU), apolipoprotein L1 (APOL1), alpha-1-B glycoprotein (A1BG), fibrinogen gamma chain (FGG), Ig alpha-1 chain C region (IGHA1), complement C6 (C6), leucine rich alpha 2 glycoprotein (LRG1), and carboxypeptidase N catalytic chain (CPN1). Eight protein spots corresponding to six unique proteins were significantly decreased in abundance in the hyperthyroid samples compared with euthyroid samples. These decreased proteins were apolipoprotein A1 (APOA1), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), plasminogen (PLG), alpha-1 antitrypsin (SERPINA1), fibrinogen beta chain (FGB), and complement C1r subcomponent (C1R). The differentially abundant proteins were investigated by ingenuity pathway analysis (IPA). The network pathway identified related to infectious disease, inflammatory disease, organismal injury and abnormalities, and the connectivity map focused around two central nodes, namely the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways. The plasma proteome of patients with hyperthyroidism revealed differences in the abundance of proteins involved in acute phase response signaling, and development of a hypercoagulable and hypofibrinolytic state. Our findings enhance our existing knowledge of the altered proteins and associated biochemical pathways in hyperthyroidism.

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Section: Discussionmentioning

confidence: 99%

Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment

2020

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“…renal glomerular diseases, allograft rejection, acute kidney injury (AKI), lupus nephritis, Fanconi syndrome and diabetes [20,22,23,24]. Elevated levels of urinary RBP4 are also observed in tuberculosis, head and neck cancers and bladder cancer [25,26,27]. It has not been yet established, whether particular concentration ranges of urinary RBP4 allow identi cation of speci c renal disorders, or help discriminate individuals with a renal/non-renal pathologies among healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

The Value of Urinary RBP4 in The Diagnosis of FSGS and other Renal Diseases.

Marek-Bukowiec

Konieczny

Ratajczyk

et al. 2020

Preprint

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BackgroundUnequivocal diagnosis of FSGS can only be made with a renal biopsy, which is an invasive, risk-associated medical procedure. The discovery of non-invasive molecular biomarkers for the diagnosis of FSGS remains an important scientific goal. This study examines the urinary proteome of FSGS patients and reference groups, in order to identify urinary protein expression alterations indicative of FSGS. Methods Urine samples were collected from subjects representing FSGS, IgA nephropathy (IgAN), clear cell renal cell carcinoma (ccRCC), chromophobe renal cell carcinoma (chRCC), and healthy control group, respectively. The samples were subjected to SWATH-MS proteomics analysis. ELISA was utilized to validate the expression level of Retinol-binding protein 4 (uRBP4) in FSGS and reference samples (IgAN, ccRCC, chRCC, prostate cancer and healthy subjects).ResultsThe MS study identified 194 (FSGS), 179 (IgAN), 271 (ccRCC), 255 (chRCC), and 275 (healthy controls) urinary proteins. The comparative proteomic analysis revealed that urinary Retinol-binding protein 4 (uRBP4) clearly discriminates FSGS from the rest of the groups. Increased levels of uRBP4 in FSGS urine specimens were also evidenced by ELISA. Significantly elevated levels of uRBP4 were also observed for IgAN, ccRCC and chRCC versus healthy individuals. ConclusionsDetermining FSGS diagnosis based on uRBP4 expression alone is not possible. Specific uRBP4 concentration cut-off can be applied to accurately distinguish individuals with renal disorder (in general) from healthy subjects. Possibly, urinary RBP4 could serve as a screening biomarker identifying people at risk of renal disorders, who should undergo more detailed diagnostics.

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“…renal glomerular diseases, allograft rejection, acute kidney injury (AKI), lupus nephritis, Fanconi syndrome and diabetes [16,18,19,20). Elevated levels of urinary RBP4 are also observed in tuberculosis, head and neck cancers and bladder cancer [21,22,23]. It has not been yet established, whether particular concentration ranges of urinary RBP4 allow identi cation of speci c renal disorders, or help discriminate individuals with a renal/non-renal pathologies among healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

The Value of Urinary RBP4 in The Diagnosis of FSGS and other Renal Diseases.

Marek-Bukowiec

Konieczny

Ratajczyk

et al. 2020

Preprint

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BackgroundFocal segmental glomerulosclerosis (FSGS) is the leading cause of chronic renal failure worldwide. Unequivocal diagnosis of FSGS can only be made with a renal biopsy, which is an invasive, risk-associated medical procedure. The discovery of non-invasive molecular biomarkers for the diagnosis of FSGS still remains an important scientific goal. This study examines the urinary proteome profile of FSGS patients and reference groups, in order to identify urinary protein expression alterations indicative of FSGS. Methods Urine samples were collected from subjects representing FSGS, IgA nephropathy (IgAN), clear cell renal cell carcinoma (ccRCC), chromophobe renal cell carcinoma (chRCC), and healthy control group, respectively. The samples were pooled and subjected to SWATH-MS proteomics analysis. ELISA was utilized to validate the expression level of Retinol-binding protein 4 (uRBP4) in 130 urine supernatant samples (21 FSGS, 20 IgAN, 31 ccRCC, 21 chRCC, 7 prostate cancer patients and 30 healthy volunteers).ResultsThe MS study identified 194 (FSGS), 179 (IgAN), 271 (ccRCC), 255 (chRCC), and 275 (healthy controls) urinary proteins. The comparative proteomic analysis revealed that Retinol-binding protein 4 clearly discriminates FSGS from the rest of the groups. Increased levels of uRBP4 in FSGS urine specimens were also detected by ELISA (FSGS vs IgAN p=0.0244, FSGS vs ccRCC p=0.004, FSGS vs chRCC p=0.013, FSGS vs prostate cancer p=0.02, FSGS vs healthy controls p<0.00001). Significantly elevated levels of uRBP4 were also observed for IgAN, ccRCC and chRCC versus healthy individuals.ConclusionsUrinary RBP4 protein is significantly upregulated in FSGS in comparison to IgAN, ccRCC, chRCC, prostate cancer patients and healthy subjects. Determining FSGS diagnosis based on uRBP4 expression alone is not possible. Specific uRBP4 concentration cut-off can be applied to accurately distinguish individuals with renal disorder (in general) from healthy subjects. Thus, urinary RBP4 could serve as a screening biomarker identifying people at risk of renal disorders, who should undergo more detailed diagnostics.

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Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures

Cited by 30 publications

References 60 publications

Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment

Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment

The Value of Urinary RBP4 in The Diagnosis of FSGS and other Renal Diseases.

The Value of Urinary RBP4 in The Diagnosis of FSGS and other Renal Diseases.

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