Processing of Serum Proteins Underlies the Mass Spectral Fingerprinting of Myocardial Infarction

Marshall, John; Kupchak, Peter; Zhu, Weimin; Yantha, Jason; Vrees, Tammy; Furesz, Shirley; Jacks, Kellie; Smith, Chris; Kireeva, Inga; Zhang, Rulin; Takahashi, Miyoko; Stanton, Eric; Jackowski, George

doi:10.1021/pr030003l

Cited by 212 publications

(356 citation statements)

References 49 publications

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“…Marshall et al have recently shown that when plasma was left sitting at room temperature for 4 or 8 h, the MALDI-TOF spectra, as recorded by a SELDI-TOF instrument, changed significantly, suggesting that many peptides were generated by proteolytic digestion ex vivo (59). The authors attributed this peptide generation to action of specific (serine) proteases, because they could block this effect with serine protease inhibitors.…”

Section: Technical Caveats and Methodological Detailsmentioning

confidence: 99%

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: Technical Caveats and Methodological Detailsmentioning

confidence: 99%

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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“…Of the 66 cases of nonmalignant disease, 63 were recognized as not cancer. This result yielded a sensitivity of 100%, specificity of 95% (87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99), and PPV of 94% (101). Although the limitations of this study design and its analysis have been discussed in some detail in the literature (103)(104)(105)(106), the potential implications of such proteomic spectrum analysis for the identification of novel tumor markers is huge.…”

Section: Trials In the Generalmentioning

confidence: 95%

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Jacobs

Menon

2004

Molecular & Cellular Proteomics

421

312

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Ovarian cancer is characterize by few early symptoms, presentation at an advanced stage, and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. During the last decade, a research effort has been directed toward improving outcomes for ovarian cancer by screening for preclinical, early stage disease using both imaging techniques and serum markers. Numerous biomarkers have shown potential in samples from clinically diagnosed ovarian cancer patients, but few have been thoroughly assessed in preclinical disease and screening. The most thoroughly investigated biomarker in ovarian cancer screening is CA125. Prospective studies have demonstrated that both CA125 and transvaginal ultrasound can detect a significant proportion of preclinical ovarian cancers, and refinements in interpretation of results have improved sensitivity and reduced the false-positive rate of screening. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from ovarian cancer is still unclear. Prospective studies of screening are in progress in both the general population and high-risk population, including the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKC-TOCS), a randomized trial involving 200,000 postmenopausal women designed to document the impact of screening on mortality. Recent advances in technology for the study of the serum proteome offer exciting opportunities for the identification of novel biomarkers or patterns of markers that will have greater sensitivity and lead time for preclinical disease than CA125. Considerable interest and controversy has been generated by initial results utilizing surface-enhanced laser desorption/ionization (SELDI) in ovarian cancer. There are challenging issues related to the design of studies to evaluate SELDI and other proteomic technology, as well as the reproducibility, sensitivity, and specificity of this new technology. Large serum banks such as that assembled in UKCTOCS, which contain preclinical samples from patients who later developed ovarian cancer and other disorders, provide a unique resource for carefully designed studies of proteomic technology. There is a sound basis for optimism that further developments in serum proteomic analysis will provide powerful methods for screening in ovarian cancer and many other diseases.

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“…Serum apo A-I, apo A-II, and their glycosylated products were found differentially expressed between atherosclerosis patients and normal controls by using SELDI-MS [249]. MALDI-MS analysis of peptides from the sera of normal and AMI subjects produced characteristic patterns that could provide an accurate diagnosis of AMI [250]. Serum alpha-B-crystallin and tropomyosin were discovered and validated as valuable biomarkers for cardiac allograft rejection [251].…”

Section: Application To Human Disease Detectionmentioning

confidence: 99%

Human body fluid proteome analysis

2006

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The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.

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Processing of Serum Proteins Underlies the Mass Spectral Fingerprinting of Myocardial Infarction

Cited by 212 publications

References 49 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

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Human body fluid proteome analysis

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