Putative protein markers in the sera of men with prostatic neoplasms

Lehrer, Steven; Roboz, John; Ding, Hu; Sun, Zhao; Diamond, Edward J.; Holland, Jason; Stone, Nelson N.; Droller, Michael J.; Stock, Richard G.

doi:10.1046/j.1464-410x.2003.04341.x

Cited by 55 publications

(31 citation statements)

References 3 publications

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“…For example, PSA can be used as a biomarker for a group of patients without cancer (PSA Ͻ 1 g/liter) and patients with histologically confirmed prostate cancer and PSA Ͼ 10 g/liter. Because free PSA and complexed PSA have molecular masses of ϳ30 kDa and 100 kDa, respectively, these masses are well within the current capabilities of mass spectrometers (43). Validation of this technology will be highly enhanced if it is shown that one of the discriminatory peaks identified in prostate cancer is PSA and its subfractions.…”

Section: Failure To Identify Established Cancer Biomarkersmentioning

confidence: 89%

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Diamandis¹

2004

Molecular & Cellular Proteomics

188

249

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Serum proteomic profiling, by using surfaced-enhanced laser desorption/ionization-time-of-flight mass spectrometry, is one of the most promising new approaches for cancer diagnostics. Exceptional sensitivities and specificities have been reported for some cancer types such as prostate, ovarian, breast, and bladder cancers. These sensitivities/specificities are far superior to those obtained by using classical cancer biomarkers. In this review, I concentrate more on questions that cast doubt on the results reported and propose experiments to investigate these questions in detail, before the technique is used at the clinic. It is clear that the method needs to be externally and thoroughly validated before clinical implementation is warranted. Molecular & Cellular Proteomics 3:367-378, 2004.Our current efforts to combat cancer are not very successful. Despite the recent spectacular advances in molecular medicine, genomics, proteomics, and translational research, mortality rates for the most prevalent cancers have not been significantly reduced. Some of the best available options to combat cancer include primary prevention, earlier diagnosis, and improved therapeutic interventions. We are now witnessing the development of new drugs against cancer that are based on rational instead of empirical designs. There is hope that some of these drugs will prove to be more effective at the clinic than older generations of medicines. In terms of primary prevention, we do not as yet have at hand any robust strategies, because the mechanisms of cancer initiation and progression are still largely unknown.One of the best strategies to combat cancer now is by early diagnosis and administration of effective treatment (1). Another approach includes close monitoring of the cancer patient after initial treatment (usually surgery) to detect early relapse and then prescribe additional therapy. A third valuable approach would be the stratification of patients into subgroups that respond better to different types of treatment (individualized therapy). Medical imaging and serum or tissue biomarkers are valuable tools for monitoring these patients in order to optimize clinical outcomes.In this review, I will concentrate on mass spectrometry as a diagnostic and cancer biomarker discovery tool. Much has been published on this technology, and excellent reviews have already been prepared (2-12). My presentation will be biased toward underlining potential limitations that have not been adequately addressed in the already existing extensive literature. MASS SPECTROMETRYMass spectrometry has been used as a diagnostic tool in clinical laboratories for many decades. This technology has been coupled with gas chromatography (GC/MS) 1 and has been used with success for the identification and quantification of relatively small molecules (with molecular mass Ͻ1,000 Da). Such molecules could be highly informative in newborn screening programs (13), toxicological and forensic applications (14), for delineating various types of inborn errors of metabolism (15...

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Section: Failure To Identify Established Cancer Biomarkersmentioning

confidence: 89%

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Diamandis¹

2004

Molecular & Cellular Proteomics

188

249

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“…The serum proteome would be expected to reflect what has been experienced or encountered by the blood during its constant perfusion through the body. SELDI-TOF MS has been demonstrated to be able to broadly explore the proteome and yield biomarkers that can be used individually or in combination to distinguish several forms of cancer from normal controls (12)(13)(14)(15). However, for exogenous exposures, the application of SELDI-TOF MS as a discovery tool to identify differentially expressed proteins has been limited.…”

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confidence: 99%

Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics

Vermeulen¹,

Lan²,

Zhang³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Benzene is an important industrial chemical and environmental contaminant that causes leukemia. To obtain mechanistic insight into benzene's mechanism of action, we examined the impact of benzene on the human serum proteome in a study of exposed healthy shoe-factory workers and unexposed controls. Two sequential studies were performed, each using sera from 10 workers exposed to benzene (overall mean benzene air level >30 ppm) and 10 controls. Serum samples were subjected to anion-exchange fractionation and bound to three types of ProteinChip arrays (Ciphergen Biosystems, Fremont, CA) [hydrophobic (H50), metal affinity (IMAC3-Cu), and cation exchange (WCX2)]. Protein-expression patterns were detected by surface-enhanced laser desorption͞ ionization (SELDI)-TOF MS. Three proteins (4.1, 7.7, and 9.3 kDa) were consistently down-regulated in exposed compared with control subjects in both studies. All proteins were highly inversely correlated with individual estimates of benzene exposure (r > 0.75). The 7.7-and 9.3-kDa proteins were subsequently identified as platelet factor (PF)4 and connective tissue activating peptide (CTAP)-III. Initial proteomic results for PF4 and CTAP-III were subsequently confirmed in a single experiment using a ProteinChiparray-based immunoassay(Ciphergen Biosystems). The altered expression of the platelet-derived CXC-chemokines (40% and 63% for PF4 and CTAP-III, respectively) could not be explained by changes in absolute platelet counts. Thus, SELDI-TOF analysis of a limited number of exposed and unexposed subjects revealed that lowered expression of PF4 and CTAP-III proteins is a potential biomarker of benzene's early biologic effects and may play a role in the immunosuppressive effects of benzene.biomarker ͉ leukemia ͉ mass spectrometry ͉ platelet ͉ molecular epidemiology

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“…[9][10][11][12][13][15][16][17][18][19][20][21]25 The most interesting discovery of the study was the finding that a SELDI-derived peak (m/z 4,462) was as effective at discriminating cancer from benign serum as the tumor markers CEA or CA19.9, while combining these three serum markers marginally improved classification. Classification could be further improved with data generated from a panel of peaks, suggesting analysis of proteomic profiles, rather than individual proteins, may yield improved diagnostic ability.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13][15][16][17][18][19][20][21]25 A potential source of error in the tissue group not present in the serum study may be sampling error. The high desmoplastic nature of CCs means the sampled tissue may miss the malignant portion of the tumor and may mainly consist of stroma rather than cholangiocytes proper.…”

Section: Discussionmentioning

confidence: 99%

“…Proteomic profiling of serum has been used with a number of other malignancies to discover potential biomarkers. 7,8 In particular, affinity-based arrays-such as the protein chips analyzed via surface-enhanced laser desorption/ionization time-offlight mass spectrometry (SELDI-TOF MS) used in this study-have been used to successfully identify malignant patterns in serum from ovarian, [9][10][11] pancreatic, [12][13][14] head and neck, 15,16 prostate, 17 transitional cell, 18 renal cell, 19,20 and breast 21 cancers. TOF-MS separates ions derived from proteins or protein fragments that are differentially detected according to their mass-to-charge ratio.…”

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confidence: 99%

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Proteomic profiling of cholangiocarcinoma: Diagnostic potential of SELDI-TOF MS in malignant bile duct stricture

et al. 2006

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Proteomic techniques promise to improve the diagnosis of cholangiocarcinoma (CC) in both tissue and serum as histological diagnosis and existing serum markers exhibit poor sensitivities. We explored the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify potential protein biomarkers of CC. Twenty-two resected CC samples were compared with adjacent noninvolved bile duct tissue. Serum from patients with CC (n ‫؍‬ 20) was compared with patients with benign disease (n ‫؍‬ 20), and healthy volunteers (n ‫؍‬ 25). Samples were analyzed on hydrophobic protein chips via SELDI-TOF MS, and classification models were developed using logistic regression and cross-validation analysis. Univariate analysis revealed 14 individual peaks differentially expressed between CC and bile duct tissue, 4 peaks between CC and benign disease, and 12 peaks between CC and sera of healthy volunteers. The 4,462 mass-to-charge serum peak had superior discriminatory ability to carbohydrate antigen 19.9 (CA19.9) and carcinoembryonic antigen ( C holangiocarcinoma (CC) is a rare but devastating neoplasm that accounts for 3% of all gastrointestinal cancers and 15% of all primary liver cancers worldwide. 1 Five thousand new cases are diagnosed on average per year in the United States, and the incidence is rising. 2 Northeast Thailand sees the highest incidence, with 96 cases per 100,000. 1 Surgical resection is the only current chance of cure, with no proven adjunctive therapy; however, this approach has a mortality rate of 5% to 10%. 3 Even with margin-free resection, 5-year survival figures only reach 20% to 40%. 3,4 Unresectable disease is usually fatal within 6 months to 1 year, and over one third of patients present at a stage too late for resection. 3 This confirms the need for earlier and more accurate diagnostic processes.At present, diagnosis of CC relies on imaging of the biliary tree with computed tomography or ultrasonography in the presence of high clinical suspicion. Tissue diagnostic confirmation is possible for intrahepatic tumors but is very difficult in more distal and more common (2/3 of cases) extrahepatic cases. These frequently present as a stricture of the common bile duct, which can be further characterized by means of endoscopic retrograde cholangio-pancreatography. 5

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Putative protein markers in the sera of men with prostatic neoplasms

Cited by 55 publications

References 3 publications

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics

Proteomic profiling of cholangiocarcinoma: Diagnostic potential of SELDI-TOF MS in malignant bile duct stricture

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