Abstract:The heterogeneous progression to the development of prostate cancer (PCa) has precluded effective early detection screens. Existing prostate cancer screening paradigms have relatively poor specificity for cancer relative to other prostate diseases, commonly benign prostatic hyperplasia (BPH). A method for discrimination of BPH, HGPIN, and PCa urine proteome was developed through testing 407 patient samples using matrix assisted laser desorption-mass spectrometry time of flight (MALDI-TOF). Urine samples were a… Show more
“…They include studies of acute kidney injury, 33,34 acute renal allograft rejection, 35-38 glomerular disease [39][40][41][42][43][44][45][46] and carcinoma of the kidney, bladder and prostate. [47][48][49] In many cases the reported biomarkers remain unidentified, although some studies have proceeded to identification of the biomarker proteins.…”
P roteomics is the study of protein expression in a tissue or biological fluid. Comparison of protein patterns in biological fluids between healthy individuals and patients with disease is increasingly being used both to discover biological markers of disease (biomarkers) and to identify biochemical processes important in disease pathogenesis. Although currently available tests for urine proteins measure either the total level of urine protein or the presence of a single protein species, emerging proteomic technologies allow simultaneous examination of the patterns of multiple urinary proteins and their correlation with individual diagnoses, response to treatment or prognosis. Analysis of the various protein constituents of urine may suggest novel, noninvasive diagnostic tests, therapeutic guidance, and prognostic information for patients and clinicians.In this review, we describe the current practice of urine protein testing and the emerging technologies that are being used for analysis of the urinary proteome.
BackgroundNormally, the low-molecular-weight proteins and albumin that are filtered from plasma into the early tubular fluid are almost completely reabsorbed and catabolized in the proximal tubules. As a result, daily urinary protein excretion is less than 150 mg/day, of which about 10 mg is albumin. In patients with physiologic proteinuria, the proteins excreted include mucoproteins (mainly Tamm-Horsfall protein), blood-group proteins, albumin, immunoglobulins, mucopolysaccharides and very small amounts of hormones and enzymes. Historically, proteinuria of more than 150 mg/day was regarded as abnormal. However, it is now appreciated that early renal disease is often characterized by low-level albuminuria (between 30 and 300 mg/day).1 This condition is termed microalbuminuria because the concentration of albumin is below the detection limit of traditional assays. Protein or albumin excretion greater than 300 mg/day represents overt proteinuria or macroalbuminuria; at this level, the result of standard urine dipstick testing becomes positive.Pathological proteinuria can be divided into 3 categories: glomerular proteinuria, tubular proteinuria and overload proteinuria.2 Glomerular proteinuria results from an increase in the permeability of the glomerular capillary wall to macromolecules (particularly albumin) and usually results from glomerular disease. Tubular proteinuria results from reduced reabsorption of proteins that are normally present in the glomerular filtrate or from excretion of proteins derived from injured tubular epithelial cells. It is usually caused by diseases of the tubulointerstitium. Overload proteinuria is due to an excess of low-molecular-weight proteins that are normally reabsorbed by the proximal tubules. These proteins are most often immunoglobulin light chains (in the plasma cell dyscrasias), although lysozyme (in myelomonocytic leukemia), myoglobin (in rhabdomyolysis) or hemoglobin (in intravascular hemolysis) may also be identified.Under normal conditions, urinary proteins exis...
“…They include studies of acute kidney injury, 33,34 acute renal allograft rejection, 35-38 glomerular disease [39][40][41][42][43][44][45][46] and carcinoma of the kidney, bladder and prostate. [47][48][49] In many cases the reported biomarkers remain unidentified, although some studies have proceeded to identification of the biomarker proteins.…”
P roteomics is the study of protein expression in a tissue or biological fluid. Comparison of protein patterns in biological fluids between healthy individuals and patients with disease is increasingly being used both to discover biological markers of disease (biomarkers) and to identify biochemical processes important in disease pathogenesis. Although currently available tests for urine proteins measure either the total level of urine protein or the presence of a single protein species, emerging proteomic technologies allow simultaneous examination of the patterns of multiple urinary proteins and their correlation with individual diagnoses, response to treatment or prognosis. Analysis of the various protein constituents of urine may suggest novel, noninvasive diagnostic tests, therapeutic guidance, and prognostic information for patients and clinicians.In this review, we describe the current practice of urine protein testing and the emerging technologies that are being used for analysis of the urinary proteome.
BackgroundNormally, the low-molecular-weight proteins and albumin that are filtered from plasma into the early tubular fluid are almost completely reabsorbed and catabolized in the proximal tubules. As a result, daily urinary protein excretion is less than 150 mg/day, of which about 10 mg is albumin. In patients with physiologic proteinuria, the proteins excreted include mucoproteins (mainly Tamm-Horsfall protein), blood-group proteins, albumin, immunoglobulins, mucopolysaccharides and very small amounts of hormones and enzymes. Historically, proteinuria of more than 150 mg/day was regarded as abnormal. However, it is now appreciated that early renal disease is often characterized by low-level albuminuria (between 30 and 300 mg/day).1 This condition is termed microalbuminuria because the concentration of albumin is below the detection limit of traditional assays. Protein or albumin excretion greater than 300 mg/day represents overt proteinuria or macroalbuminuria; at this level, the result of standard urine dipstick testing becomes positive.Pathological proteinuria can be divided into 3 categories: glomerular proteinuria, tubular proteinuria and overload proteinuria.2 Glomerular proteinuria results from an increase in the permeability of the glomerular capillary wall to macromolecules (particularly albumin) and usually results from glomerular disease. Tubular proteinuria results from reduced reabsorption of proteins that are normally present in the glomerular filtrate or from excretion of proteins derived from injured tubular epithelial cells. It is usually caused by diseases of the tubulointerstitium. Overload proteinuria is due to an excess of low-molecular-weight proteins that are normally reabsorbed by the proximal tubules. These proteins are most often immunoglobulin light chains (in the plasma cell dyscrasias), although lysozyme (in myelomonocytic leukemia), myoglobin (in rhabdomyolysis) or hemoglobin (in intravascular hemolysis) may also be identified.Under normal conditions, urinary proteins exis...
“…These include the use of 2D-DIGE as a means to identify serum markers for the differentiation of more aggressive prostate cancer [Byrne et al, 2009]. Similar studies have been performed in urine samples to develop a ''urine proteome'' for the identification of prostate cancer [M'Koma et al, 2007]. The idea of a fingerprint for the detection and classification of prostate cancer is still one that holds much promise but as of yet, needs further investigation and validation.…”
The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood-based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease.
“…Furthermore, MALDI-MS has been employed in the detection of biomarkers in kidney disease (16), genitourinary tumours, including bladder (17) and prostate cancer (18), and tumours outwith the genitourinary tract, including pancreatic (19) and colon cancer (20). In this preliminary study, MS was used to demonstrate that urine from cachectic GO cancer patients contained significantly more protein species than urine from weight-stable GO cancer patients and healthy controls, in the absence of an elevated CK level.…”
Abstract. Increased membrane permeability and myofibrillar protein breakdown are established features of cancer cachexia. Proteins released from cachectic muscle may be excreted in urine to act as biomarkers of the cachectic process. Onedimensional SDS polyacrylamide gel electrophoresis followed by matrix-assisted laser desorption/ionisation or liquid chromatography tandem mass spectrometry was used to compare the protein content of urine from cachectic (>10% weight loss) (n=8) and weight-stable (n=8) gastro-oesophageal cancer patients and healthy controls (n=8). Plasma creatine kinase concentration was used as a marker of gross muscle breakdown. The number of protein species identified in cachectic samples (median 42; range 28-61; total 199) was greater than that identified in weight-stable cancer (median 15; range 9-28; total 79) and control samples (median 12.5; range 5-18; total 49) (P<0.001). Many of the proteins identified have not been reported previously in the urine of cancer patients. Proteins identified specifically in cachectic samples included muscle (myosin species), cytoskeletal (·-spectrin; nischarin) and microtubule-associated proteins (microtubule-actin crosslinking factor; microtubule-associated protein-1B; bullous pemphigoid antigen 1), whereas immunoglobulin κ-light chain and zinc ·-2 glycoprotein appeared to represent markers of cancer. The presence of myosin in urine (without an increase in plasma creatine kinase) is consistent with a specific loss of myosin as part of the cachectic process. Urinary proteomics using mass spectrometry can identify muscle-specific and non-muscle-specific candidate biomarkers of cancer cachexia.
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