SELDI-TOF MS Whole Serum Proteomic Profiling with IMAC Surface Does Not Reliably Detect Prostate Cancer

Abstract

Background: The analysis of bodily fluids using SELDI-TOF MS has been reported to identify signatures of spectral peaks that can be used to differentiate patients with a specific disease from normal or control patients. This report is the 2nd of 2 companion articles describing a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify prostatic adenocarcinoma. Methods: We sought to derive a decision algorithm for classification of prostate cancer from SELDI-TOF MS spectral data from a new retrospective sample cohort of 400 specimens. This new cohort was selected to minimize possible confounders identified in the previous study described in the companion paper. Results: The resulting new classifier failed to separate patients with prostate cancer from biopsy-negative controls; nor did it separate patients with prostate cancer with Gleason scores <7 from those with Gleason scores ≥7. Conclusions: In this, the 2nd stage of our planned validation process, the SELDI-TOF MS–based protein expression profiling approach did not perform well enough to advance to the 3rd (prospective study) stage. We conclude that the results from our previous studies—in which differentiation between prostate cancer and noncancer was demonstrated—are not generalizable. Earlier study samples likely had biases in sample selection that upon removal, as in the present study, resulted in inability of the technique to discriminate cancer from noncancer cases.

The Value of Surface Enhanced Laser Desorption/Ionization-Time of Flight Mass Spectrometry at the Diagnosis of Non-Small Cell Lung Cancer: A Systematic Review

“…However, none of these biomarkers are ideal early detection markers because of their low specificity and/or sensitivity (4 However, for prospective studies, SELDI-TOF-MS experiments are described presenting their respective advantages and limitations. Many reviews drove validation of these biomarkers quite challenging (6,37). All challenges that should be undertaken to avoid any bias, to maximize reproducibility and detection sensitivity, with the final aim to find relevant, specific, and robust biomarkers are addressed (6).…”

Proteomics in Peritoneal Dialysis

“…The SELDI technology draws a lot of interest because of its ease of use and its high throughput for biomarker discovery. However, the low-resolution of the mass spectrometer, the large amount of variability between labs, and its lack of reproducibility, hamper its potential clinical application (McLerran et al 2008). …”

Endoprotease Profiling with Double-Tagged Peptide Substrates: A New Diagnostic Approach in Oncology

“…High-throughput mass spectrometry (MS) 5 can generate peptide patterns from hundreds of specimens that can be further analyzed with bioinformatics algorithms to enable early diagnosis and improve therapeutic monitoring of patients (1 ). However, the clinical proteomic profiling approach is fraught with controversy (2 ).…”

“…For the analysis of serum specimens preanalytical variables have a major impact on profiling experiments by partially overriding disease-related peptide patterns (3 ) or even completely abolishing meaningful data interpretation (4 ). Furthermore, there are inherent difficulties in reproducing results from different studies (5,6 ), and therefore clinical proteomic profiling has not matured to the point of being introduced into routine diagnostic procedures. However, under strictly controlled conditions, the proteolytic fragments from highly abundant endogenous serum proteins generate distinct peptide patterns that are suitable as surrogate marker for disease-specific proteolytic activity (7 ).…”