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Article ; Online: Biomarkers for the diagnosis of new and recurrent prostate cancer.

Sardana, Girish / Diamandis, Eleftherios P

2012 Volume 6, Issue 5, Page(s) 587–596

Abstract: Prostate cancer is the most prevalent cancer in men and can be managed effectively if diagnosed early and monitored. Currently, prostate-specific antigen testing in conjunction with a digital rectal exam has been utilized for screening at-risk men. ... ...

Abstract	Prostate cancer is the most prevalent cancer in men and can be managed effectively if diagnosed early and monitored. Currently, prostate-specific antigen testing in conjunction with a digital rectal exam has been utilized for screening at-risk men. However, the lack of specificity of prostate-specific antigen as a marker for prostate cancer combined with the asymptomatic and slow-growing nature of prostate tumors has resulted in many men being overdiagnosed and subjected to surgery or treatment with adverse side effects. The focus in the research community currently has been on discovering noninvasive surrogate markers such as proteins, circulating tumor cells and nucleic acids in the blood or urine of patients with prostate cancer. These markers, in combination with prostate-specific antigen, are providing promise that a personalized multiparametric approach to prostate cancer diagnosis and monitoring will aid in managing this disease.
MeSH term(s)	Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Computational Biology ; Humans ; Male ; Neoplastic Cells, Circulating/metabolism ; Neoplastic Cells, Circulating/pathology ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Recurrence
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2012-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2481014-9
ISSN	1752-0371 ; 1752-0363
ISSN (online)	1752-0371
ISSN	1752-0363
DOI	10.2217/bmm.12.72
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Article ; Online: The kallikrein family of proteins as urinary biomarkers for the detection of prostate cancer.

Sardana, Girish / Diamandis, Eleftherios P

Clinical biochemistry

2009 Volume 42, Issue 13-14, Page(s) 1483–1486

Abstract: Background: Several urinary biomarkers have been assessed as showing a discriminatory ability to differentially diagnose prostate cancer, albeit with manipulation of the prostate. Here we examine the clinical utility of multiple members of the ... ...

Abstract	Background: Several urinary biomarkers have been assessed as showing a discriminatory ability to differentially diagnose prostate cancer, albeit with manipulation of the prostate. Here we examine the clinical utility of multiple members of the kallikrein family of proteins in non-manipulative urinary biomarker testing. Methods: Forty urine samples were collected from patients admitted for urological examination. Twenty, with a confirmed benign diagnosis and 20 with prostate cancer. The levels of 14 kallikrein proteins were measured in patient's urine and normalized for creatinine. Results: Ten of the 14 kallikreins tested had detectable levels in urine. However, none showed statistical significance in discriminating patients. Serum PSA was superior to urine PSA and other urinary kallikreins in separating patients with and without prostate cancer. Conclusions: We were unable to distinguish men with and without prostate cancer using multiple kallikreins as urinary biomarkers. These results highlight the difficulties in diagnosing prostate cancer via urine testing for soluble biomarkers.
MeSH term(s)	Aged ; Biomarkers, Tumor/urine ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Humans ; Kallikreins/urine ; Male ; Middle Aged ; Prostate-Specific Antigen/blood ; Prostatic Hyperplasia/blood ; Prostatic Hyperplasia/diagnosis ; Prostatic Hyperplasia/urine ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/urine ; Protein Isoforms/urine ; Sensitivity and Specificity
Chemical Substances	Biomarkers, Tumor ; Protein Isoforms ; Kallikreins (EC 3.4.21.-) ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2009-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2009.06.015
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Article: Acute venous sinus thrombosis after chickenpox infection.

Sardana, Vijay / Mittal, Lal Chand / Meena, S R / Sharma, Deepti / Khandelwal, Girish

The Journal of the Association of Physicians of India

2014 Volume 62, Issue 8, Page(s) 741–743

Abstract: Background: Chickenpox is one of the classic childhood diseases. Recently chicken pox has been reported in adults with more severe systemic and neurological complications. Cerebral venous thrombosis (CVT) is a life threatening disorder if not treated in ...

Abstract	Background: Chickenpox is one of the classic childhood diseases. Recently chicken pox has been reported in adults with more severe systemic and neurological complications. Cerebral venous thrombosis (CVT) is a life threatening disorder if not treated in time. We report a patient with post varicella CVT as a rare complication of primary Varicella zoster virus. Case report: Vasculitic arterial infarction is known while venous stroke has rarely been reported with Varicella-zoster virus infection. Here, we report an immunocompetent 30 yr old male who developed chickenpox after contact with his daughter two month back. He presented with acute neurological deficit, one week after onset of skin lesion. MR venography revealed non-visualisation of left transverse sinus and left sigmoid sinus suggestive of venous sinus thrombosis. Conclusion: Varicella infection is rarely associated with venous sinus thrombosis. Possibly hypercoagulable state produced by the infection or direct invasion of virus in venous endothelial wall with subsequent damage to endothelium leading to thrombosis could be the cause.
MeSH term(s)	Adult ; Chickenpox/complications ; Humans ; Male ; Sinus Thrombosis, Intracranial/etiology
Language	English
Publishing date	2014-08
Publishing country	India
Document type	Case Reports ; Journal Article
ZDB-ID	800766-4
ISSN	0004-5772
ISSN	0004-5772
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Article ; Online: Emerging biomarkers for the diagnosis and prognosis of prostate cancer.

Sardana, Girish / Dowell, Barry / Diamandis, Eleftherios P

Clinical chemistry

2008 Volume 54, Issue 12, Page(s) 1951–1960

Abstract: Background: Early detection of prostate cancer (CaP), the most prevalent cancer and the second-leading cause of death in men, has proved difficult, and current detection methods are inadequate. Prostate-specific antigen (PSA) testing is a significant ... ...

Abstract	Background: Early detection of prostate cancer (CaP), the most prevalent cancer and the second-leading cause of death in men, has proved difficult, and current detection methods are inadequate. Prostate-specific antigen (PSA) testing is a significant advance for early diagnosis of patients with CaP. Content: PSA is produced almost exclusively in the prostate, and abnormalities of this organ are frequently associated with increased serum concentrations. Because of PSA's lack of specificity for CaP, however, many patients undergo unnecessary biopsies or treatments for benign or latent tumors, respectively. Thus, a more specific method of CaP detection is required to augment or replace screening with PSA. The focus recently has been on creating cost-effective assays for circulating protein biomarkers in the blood, but because of the heterogeneity of CaP, it has become clear that this effort will be a formidable challenge. Each marker will require proper validation to ensure clinical utility. Although much work has been done on variations of the PSA test (i.e., velocity, density, free vs bound, proisoforms) with limited usefulness, there are many emerging markers at various stages of development that show some promise for CaP diagnosis. These markers include kallikrein-related peptidase 2 (KLK2), early prostate cancer antigen (EPCA), PCA3, hepsin, prostate stem cell antigen, and alpha-methylacyl-CoA racemase (AMACR). We review biomarkers under investigation for the early diagnosis and management of prostate cancer. Summary: It is hoped that the use of panels of markers can improve CaP diagnosis and prognosis and help predict the therapeutic response in CaP patients.
MeSH term(s)	Antigens, Neoplasm/blood ; Biomarkers, Tumor/blood ; GPI-Linked Proteins ; Humans ; Male ; Membrane Glycoproteins/blood ; Neoplasm Proteins/blood ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/diagnosis ; Racemases and Epimerases/blood ; Serine Endopeptidases/blood ; Tissue Kallikreins/blood
Chemical Substances	Antigens, Neoplasm ; Biomarkers, Tumor ; GPI-Linked Proteins ; Membrane Glycoproteins ; Neoplasm Proteins ; PSCA protein, human ; early prostate cancer antigen, human ; prostate cancer antigen 3, human ; Serine Endopeptidases (EC 3.4.21.-) ; hepsin (EC 3.4.21.-) ; Tissue Kallikreins (EC 3.4.21.35) ; Prostate-Specific Antigen (EC 3.4.21.77) ; Racemases and Epimerases (EC 5.1.-) ; alpha-methylacyl-CoA racemase (EC 5.1.99.4)
Language	English
Publishing date	2008-10-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1373/clinchem.2008.110668
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Article ; Online: Phosphorylation of IGFBP-1 at discrete sites elicits variable effects on IGF-I receptor autophosphorylation.

Abu Shehab, Majida / Iosef, Cristiana / Wildgruber, Robert / Sardana, Girish / Gupta, Madhulika B

Endocrinology

2013 Volume 154, Issue 3, Page(s) 1130–1143

Abstract: We previously demonstrated that hypoxia and leucine deprivation cause hyperphosphorylation of IGF-binding protein-1 (IGFBP-1) at discrete sites that markedly enhanced IGF-I affinity and inhibited IGF-I-stimulated cell growth. In this study we ... ...

Abstract	We previously demonstrated that hypoxia and leucine deprivation cause hyperphosphorylation of IGF-binding protein-1 (IGFBP-1) at discrete sites that markedly enhanced IGF-I affinity and inhibited IGF-I-stimulated cell growth. In this study we investigated the functional role of these phosphorylation sites using mutagenesis. We created three IGFBP-1 mutants in which individual serine (S119/S169/S98) residues were substituted with alanine and S101A was recreated for comparison. The wild-type (WT) and mutant IGFBP-1 were expressed in Chinese hamster ovary cells and IGFBP-1 in cell media was isolated using isoelectric-focusing-free-flow electrophoresis. BIACore analysis indicated that the changes in IGF-I affinity for S98A and S169A were moderate, whereas S119A greatly reduced the affinity of IGFBP-1 for IGF-I (100-fold, P < .0001). Similar results were obtained with S101A. The IGF-I affinity changes of the mutants were reflected in their ability to inhibit IGF-I-induced receptor autophosphorylation. Employing receptor-stimulation assay using IGF-IR-overexpressing P6 cells, we found that WT-IGFBP-1 inhibited IGF-IRβ autophosphorylation (~2-fold, P < .001), possibly attributable to sequestration of IGF-I. Relative to WT, S98A and S169A mutants did not inhibit receptor autophosphorylation. S119A, on the other hand, greatly stimulated the receptor (2.3-fold, P < .05). The data with S101A matched S119A. In summary, we show that phosphorylation at S98 and S169 resulted in milder changes in IGF-I action; nonetheless most dramatic inhibitory effects on the biological activity of IGF-I were due to IGFBP-1 phosphorylation at S119. Our results provide novel demonstration that IGFBP-1 phosphorylation at S119 can enhance affinity for IGF-I possibly through stabilization of the IGF-IGFBP-1 complex. These data also propose that the synergistic interaction of distinct phosphorylation sites may be important in eliciting more pronounced effects on IGF-I affinity that needs further investigation.
MeSH term(s)	Amino Acid Substitution ; Animals ; BALB 3T3 Cells ; Binding Sites/genetics ; CHO Cells ; Cricetinae ; Cricetulus ; Humans ; Insulin-Like Growth Factor Binding Protein 1/chemistry ; Insulin-Like Growth Factor Binding Protein 1/genetics ; Insulin-Like Growth Factor Binding Protein 1/metabolism ; Kinetics ; Mice ; Mutagenesis, Site-Directed ; Phosphorylation ; Receptor, IGF Type 1/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism
Chemical Substances	IGFBP1 protein, human ; Insulin-Like Growth Factor Binding Protein 1 ; Recombinant Proteins ; Receptor, IGF Type 1 (EC 2.7.10.1)
Language	English
Publishing date	2013-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2012-1962
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Article ; Online: Identification and quantification of peptides and proteins secreted from prostate epithelial cells by unbiased liquid chromatography tandem mass spectrometry using goodness of fit and analysis of variance.

Florentinus, Angelica K / Bowden, Peter / Sardana, Girish / Diamandis, Eleftherios P / Marshall, John G

Journal of proteomics

2012 Volume 75, Issue 4, Page(s) 1303–1317

Abstract: The proteins secreted by prostate cancer cells (PC3(AR)6) were separated by strong anion exchange chromatography, digested with trypsin and analyzed by unbiased liquid chromatography tandem mass spectrometry with an ion trap. The spectra were matched to ... ...

Abstract	The proteins secreted by prostate cancer cells (PC3(AR)6) were separated by strong anion exchange chromatography, digested with trypsin and analyzed by unbiased liquid chromatography tandem mass spectrometry with an ion trap. The spectra were matched to peptides within proteins using a goodness of fit algorithm that showed a low false positive rate. The parent ions for MS/MS were randomly and independently sampled from a log-normal population and therefore could be analyzed by ANOVA. Normal distribution analysis confirmed that the parent and fragment ion intensity distributions were sampled over 99.9% of their range that was above the background noise. Arranging the ion intensity data with the identified peptide and protein sequences in structured query language (SQL) permitted the quantification of ion intensity across treatments, proteins and peptides. The intensity of 101,905 fragment ions from 1421 peptide precursors of 583 peptides from 233 proteins separated over 11 sample treatments were computed together in one ANOVA model using the statistical analysis system (SAS) prior to Tukey-Kramer honestly significant difference (HSD) testing. Thus complex mixtures of proteins were identified and quantified with a high degree of confidence using an ion trap without isotopic labels, multivariate analysis or comparing chromatographic retention times.
MeSH term(s)	14-3-3 Proteins/metabolism ; Algorithms ; Analysis of Variance ; Chromatography, Liquid/methods ; Epithelial Cells/metabolism ; False Positive Reactions ; Humans ; Ions ; Male ; Models, Statistical ; Peptides/chemistry ; Prostate/metabolism ; Reproducibility of Results ; Software ; Tandem Mass Spectrometry/methods
Chemical Substances	14-3-3 Proteins ; Ions ; Peptides
Language	English
Publishing date	2012-02-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2011.11.002
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Article: Discovery of candidate tumor markers for prostate cancer via proteomic analysis of cell culture-conditioned medium.

Sardana, Girish / Marshall, John / Diamandis, Eleftherios P

Clinical chemistry

2007 Volume 53, Issue 3, Page(s) 429–437

Abstract: Objective: Prostate-specific antigen measurement, widely used for early detection of prostate cancer (CaP), suffers from low specificity. Additional tumor markers are needed for the early detection of clinically relevant CaP. Our objective was to ... ...

Abstract	Objective: Prostate-specific antigen measurement, widely used for early detection of prostate cancer (CaP), suffers from low specificity. Additional tumor markers are needed for the early detection of clinically relevant CaP. Our objective was to perform a qualitative proteomic analysis of conditioned medium (CM) from the CaP cell line PC3(AR)(6). Methods: We used a roller bottle culture system to culture the PC3(AR)(6) cell line in chemically defined serum-free medium for 14 days. By using strong anion-exchange chromatography, we fractionated the CM and trypsinized the fractions. The tryptic peptides were further fractionated by reversed-phase C-18 chromatography before being subjected to electrospray ionization tandem mass spectrometry. We used MASCOT software to search the mass spectra generated and organized identified proteins based on their genome ontology classification of cellular location. We used an immunoassay to measure a newly identified secreted protein, Mac-2BP, and kallikreins 5, 6, and 11 in serum samples from CaP patients and healthy men. Results: We classified 262 proteins according to cellular location; the sample was found to contain a significant proportion of secreted (23%) and membrane (16%) proteins. In a proportion of cancer patients compared with healthy men, we determined by ELISA that serum concentrations of a novel candidate biomarker Mac-2BP were increased. Conclusions: These identified proteins, and possibly many others found in the CM, may have utility as novel CaP biomarkers.
MeSH term(s)	Antigens, Neoplasm/analysis ; Biomarkers, Tumor/analysis ; Carrier Proteins/analysis ; Cell Line, Tumor ; Culture Media, Conditioned ; False Positive Reactions ; Glycoproteins/analysis ; Humans ; Immunoassay ; Kallikreins/analysis ; Male ; Prostate-Specific Antigen/analysis ; Prostatic Neoplasms/diagnosis ; Proteome/analysis ; Proteomics ; Serine Endopeptidases/analysis ; Software ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry
Chemical Substances	Antigens, Neoplasm ; Biomarkers, Tumor ; Carrier Proteins ; Culture Media, Conditioned ; Glycoproteins ; LGALS3BP protein, human ; Proteome ; trypsin-like serine protease ; KLK5 protein, human (EC 3.4.21.-) ; KLK6 protein, human (EC 3.4.21.-) ; Kallikreins (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-) ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2007-01-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1373/clinchem.2006.077370
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Article ; Online: Determination of the association of urine prostate specific antigen levels with anthropometric variables in children aged 5-14 years.

Efthimiou, Ioannis / Ferentinos, Georgios / Tsachouridis, Georgios / Sardana, Girish / Diamandis, Eleftherios

International braz j urol : official journal of the Brazilian Society of Urology

2009 Volume 36, Issue 2, Page(s) 202–7; discussion 207–8

Abstract: Purpose: Calculation of PSA is possible in human fluids even if it presents in very low concentrations with the help of hypersensitive immunodiagnostic methods. The periurethral glands represent one of the potential sources of urine prostate specific ... ...

Abstract	Purpose: Calculation of PSA is possible in human fluids even if it presents in very low concentrations with the help of hypersensitive immunodiagnostic methods. The periurethral glands represent one of the potential sources of urine prostate specific antigen (uPSA) in both sexes but the purpose of studying PSA levels in children is still unclear in the literature. In this pilot study we studied uPSA in a small cohort of normal, pre and post pubertal children, in relation to standard anthropometric variables. Materials and methods: The study cohort consisted of 58 children 5-14 years old (42 boys/16 girls). Height, weight, body mass index (BMI) and the respective stature-for-age, weight-for-age and BMI-for-age percentiles of the sample were determined. uPSA levels were measured using a third generation immunodiagnostic method (DPC Immulite that has a lower limit of detection of 3 ng/L. When levels of PSA were above the upper limit of detection, uPSA levels were assessed using the ROCHE technique. Results: uPSA levels tend to be higher in male than female children (p = 0.091, linear regression analysis). uPSA was measurable only in 3/16 girls (18.75%). Measurable uPSA was found in 18/42 boys (42.8%). The range of urine PSA in boys was 0-161000 ng/L (mean 10561.9 +/- 31830.48 ng/L). Statistical analysis with linear regression showed correlation with height and age in boys. Conclusions: The use of hypersensitive assays allows calculation of uPSA in childhood. The values of this variable are measurable in both sexes and related with gender. In boys, uPSA was correlated with age and height but not with other variables tested. Further studies are required to clarify this field.
MeSH term(s)	Adolescent ; Body Constitution/physiology ; Body Height/physiology ; Body Mass Index ; Body Weight/physiology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Linear Models ; Male ; Pilot Projects ; Prostate-Specific Antigen/urine ; Puberty/physiology
Chemical Substances	Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2009-05-07
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2206649-4
ISSN	1677-6119 ; 1677-5538
ISSN (online)	1677-6119
ISSN	1677-5538
DOI	10.1590/s1677-55382010000200011
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Article ; Online: Determination of the association of urine prostate specific antigen levels with anthropometric variables in children aged 5-14 years

Ioannis Efthimiou / Georgios Ferentinos / Georgios Tsachouridis / Girish Sardana / Eleftherios Diamandis

International Brazilian Journal of Urology, Vol 36, Iss 2, Pp 202-

2010 Volume 208

Abstract: PURPOSE: Calculation of PSA is possible in human fluids even if it presents in very low concentrations with the help of hypersensitive immunodiagnostic methods. The periurethral glands represent one of the potential sources of urine prostate specific ... ...

Abstract	PURPOSE: Calculation of PSA is possible in human fluids even if it presents in very low concentrations with the help of hypersensitive immunodiagnostic methods. The periurethral glands represent one of the potential sources of urine prostate specific antigen (uPSA) in both sexes but the purpose of studying PSA levels in children is still unclear in the literature. In this pilot study we studied uPSA in a small cohort of normal, pre and post pubertal children, in relation to standard anthropometric variables. MATERIALS AND METHODS: The study cohort consisted of 58 children 5-14 years old (42 boys/16 girls). Height, weight, body mass index (BMI) and the respective stature-for-age, weight-for-age and BMI-for-age percentiles of the sample were determined. uPSA levels were measured using a third generation immunodiagnostic method (DPC Immulite®) that has a lower limit of detection of 3 ng/L. When levels of PSA were above the upper limit of detection, uPSA levels were assessed using the ROCHE technique. RESULTS: uPSA levels tend to be higher in male than female children (p = 0.091, linear regression analysis). uPSA was measurable only in 3/16 girls (18.75%). Measurable uPSA was found in 18/42 boys (42.8%). The range of urine PSA in boys was 0-161000 ng/L (mean 10561.9 ± 31830.48 ng/L). Statistical analysis with linear regression showed correlation with height and age in boys. CONCLUSIONS: The use of hypersensitive assays allows calculation of uPSA in childhood. The values of this variable are measurable in both sexes and related with gender. In boys, uPSA was correlated with age and height but not with other variables tested. Further studies are required to clarify this field.
Keywords	prostate-specific antigen ; child ; urine ; Diseases of the genitourinary system. Urology ; RC870-923 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Urology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2010-04-01T00:00:00Z
Publisher	Sociedade Brasileira de Urologia
Document type	Article ; Online
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Article: Proteomic analysis of conditioned media from the PC3, LNCaP, and 22Rv1 prostate cancer cell lines: discovery and validation of candidate prostate cancer biomarkers.

Sardana, Girish / Jung, Klaus / Stephan, Carsten / Diamandis, Eleftherios P

Journal of proteome research

2008 Volume 7, Issue 8, Page(s) 3329–3338

Abstract: Early detection of prostate cancer is problematic due to the lack of a marker that has high diagnostic sensitivity and specificity. The prostate specific antigen (PSA) test, in combination with digital rectal examination, is the gold standard for ... ...

Abstract	Early detection of prostate cancer is problematic due to the lack of a marker that has high diagnostic sensitivity and specificity. The prostate specific antigen (PSA) test, in combination with digital rectal examination, is the gold standard for prostate cancer diagnosis. However, this modality suffers from low specificity. Therefore, specific markers for clinically relevant prostate cancer are needed. Our objective was to proteomically characterize the conditioned media from three human prostate cancer cell lines of differing origin [PC3 (bone metastasis), LNCaP (lymph node metastasis), and 22Rv1 (localized to prostate)] to identify secreted proteins that could serve as novel prostate cancer biomarkers. Each cell line was cultured in triplicate, followed by a bottom-up analysis of the peptides by two-dimensional chromatography and tandem mass spectrometry. Approximately, 12% (329) of the proteins identified were classified as extracellular and 18% (504) as membrane-bound among which were known prostate cancer biomarkers such as PSA and KLK2. To select the most promising candidates for further investigation, tissue specificity, biological function, disease association based on literature searches, and comparison of protein overlap with the proteome of seminal plasma and serum were examined. On the basis of this, four novel candidates, follistatin, chemokine (C-X-C motif) ligand 16, pentraxin 3 and spondin 2, were validated in the serum of patients with and without prostate cancer. The proteins presented in this study represent a comprehensive sampling of the secreted and shed proteins expressed by prostate cancer cells, which may be useful as diagnostic, prognostic or predictive serological markers for prostate cancer.
MeSH term(s)	Biomarkers, Tumor/analysis ; Biomarkers, Tumor/blood ; Bone Neoplasms/chemistry ; Bone Neoplasms/secondary ; Breast Neoplasms/chemistry ; Cation Exchange Resins ; Cell Line, Tumor ; Chromatography, Liquid/methods ; Computational Biology ; Culture Media, Conditioned/chemistry ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Lymphatic Metastasis ; Male ; Prostate/chemistry ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/chemistry ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/pathology ; Proteomics ; Reproducibility of Results ; Tandem Mass Spectrometry
Chemical Substances	Biomarkers, Tumor ; Cation Exchange Resins ; Culture Media, Conditioned ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2008-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078618-9
ISSN	1535-3893
ISSN	1535-3893
DOI	10.1021/pr8003216
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