SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer.
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 > or =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.
McLerran
Dale
D
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Grizzle
William E
WE
Feng
Ziding
Z
Thompson
Ian M
IM
Bigbee
William L
WL
Cazares
Lisa H
LH
Chan
Daniel W
DW
Dahlgren
Jackie
J
Diaz
Jose
J
Kagan
Jacob
J
Lin
Daniel W
DW
Malik
Gunjan
G
Oelschlager
Denise
D
Partin
Alan
A
Randolph
Timothy W
TW
Sokoll
Lori
L
Srivastava
Shiv
S
Srivastava
Sudhir
S
Thornquist
Mark
M
Troyer
Dean
D
Wright
George L
GL
Zhang
Zhen
Z
Zhu
Liu
L
Semmes
O John
OJ
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D014408:Biomarkers, Tumor / Q000097:blood*; D001800:Blood Specimen Collection; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D040901:Proteomics; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen