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Diagnostic Proteomics: Back to Basics?

Department of Pathology and Laboratory Medicine, University of Pennsylvania, 7.103 Founders, 3400 Spruce St., Philadelphia, PA 19104, E-mail srmaster@mail.med.upenn.edu

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The recent emergence of methods for rapidly profiling large numbers of protein markers by use of mass spectrometry (MS) has raised hopes for the rapid identification of novel cancer biomarkers (1). In particular, MS-based assays using surface-enhanced laser desorption/ionization (SELDI) have been used to compare serum proteomic patterns from healthy and diseased individuals in hopes of finding diagnostic signatures that can be adapted for use in the clinical laboratory. Early investigations in ovarian cancer patients suggested that panels of anonymous markers might substantially advance our current diagnostic capabilities (2)(3), although subsequent criticism has been directed at the primary data from these studies (4)(5) as well as at the SELDI time-of-flight (TOF) profiling approach itself (6)(7) [for summaries of this ongoing controversy, see Refs. (8)(9)]. Specific questions have been raised regarding the reproducibility of SELDI-TOF spectra, possible changes in protocols or inadequate calibration, and the ability of SELDI to detect low-abundance tumor markers. Additionally, observations that spectra can vary based on analytical factors such as the time of processing have been noted during large profiling experiments (10).

Several of these issues have recently been addressed through the combined efforts of investigators in the National Cancer Institute–sponsored Early Detection Research Network (EDRN). This group has undertaken a systematic assessment of the interlaboratory reproducibility of SELDI-TOF measurements along with their potential applicability to prostate cancer diagnosis. Their initial results demonstrated that relevant portions of SELDI-TOF profiles can be measured reproducibly and used to distinguish a reference set of prostate cancer cases from controls (11). This study was an encouraging step toward defining the analytical reproducibility of serum proteome profiling, although it highlighted the need . . . [Full Text of this Article]

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