SELDI‐TOF MS versus prostate specific antigen analysis of prospective plasma samples in a nested case–control study of prostate cancer

Abstract

There is an urgent need for better biomarkers for detection of clinically significant prostate cancer (PCa). Recent studies suggest that surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) analysis of serum may provide diagnostic information. The aim of this study was to investigate if PCa cases could be identified by applying predefined SELDI-TOF analysis conditions on prospectively, uniformly collected plasma samples from PCa cases and matched controls. Prospective samples from 387 incident PCa cases and an equal number of controls, matched for age and time for recruitment, were analyzed by SELDI-TOF MS (IMAC30/Cu chip) and multivariate classification analysis. Prospective prostate specific antigen levels were subjected to ROC curve analysis giving an AUC of 0.87 for the total cohort with a median lag time between blood sampling and diagnosis of 6.1 years. No markers were found by SELDI-TOF MS that significantly discriminated between cases and controls in the total cohort or in subanalysis of cases with less than 2 years between blood donation and diagnosis (n 5 42). Cases with aggressive disease at the time of diagnosis who gave blood less than 4 years prior to diagnosis (n 5 23) could however be separated from their controls (sensitivity 70%, specificity 83%) by a model based on SELDI-TOF MS and OPLS-DA data analysis. We were thus not able to confirm previous results with SELDI-TOF MS identifying men with PCa from healthy individuals, but we report an optimal experimental set-up for verification of markers for early detection of cancer in prospectively collected samples. ' 2007 Wiley-Liss, Inc.Key words: proteomics; prospective; prostate cancer; plasma; PSA Prostate cancer (PCa) is the most common cancer among men in many Western countries including Sweden.1 More than 9,000 Swedish men are diagnosed annually with PCa and the incidence is rapidly increasing.2 Because of testing for levels of prostate specific antigen (PSA) in serum, demographics of PCa cases is rapidly changing, cases today are younger than previously, they have smaller tumors and thus many more men are amenable to receive curative treatment. However, the specificity for the PSA test is low, due to a large overlap between PCa and benign disease, and a majority of men with moderately elevated levels of PSA are therefore not diagnosed with PCa at biopsy.3 Furthermore, a large fraction of men diagnosed with PCa today will have a cancer that is unlikely to progress for many years. 4 There is thus an urgent need for better biomarkers for detection of clinically significant PCa.Proteomic techniques applied to serum or plasma may provide valuable information about protein markers or patterns of markers, which could possibly be used to improve cancer detection.5 Serum protein profiling with surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) has been shown to detect cancer at several sites, including PCa (reviewed in Ref. 6.) Several rather small case control studies ha...

Identification of serum biomarkers for lung cancer using magnetic bead-based SELDI-TOF-MS

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Detection and identification of potential biomarkers of breast cancer

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A comparative study on proteomics between LNCap and DU145 cells by quantitative detection and SELDI analysis

“…Moreover, some abnormal proteins had been discovered in serums of cancer patients [4] , but their practical value had not been fully elucidated [5][6][7][8] .…”

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