Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: sources of sample bias.
BACKGROUND
This report and a companion report describe a validation of the ability of serum proteomic profiling via SELDI-TOF mass spectrometry to detect prostatic cancer. Details of this 3-stage process have been described. This report describes the development of the algorithm and results of the blinded test for stage 1.


METHODS
We derived the decision algorithm used in this study from the analysis of serum samples from patients with prostate cancer (n = 181) and benign prostatic hyperplasia (BPH) (n = 143) and normal controls (n = 220). We also derived a validation test set from a separate, geographically diverse set of serum samples from 42 prostate cancer patients and 42 controls without prostate cancer. Aliquots were subjected to randomization and blinded analysis, and data from each laboratory site were subjected to the decision algorithm and decoded.


RESULTS
Using the data collected from the validation test set, the decision algorithm was unsuccessful in separating cancer from controls with any predictive utility. Analysis of the experimental data revealed potential sources of bias.


CONCLUSIONS
The ability of the decision algorithm to successfully differentiate between prostate cancer, BPH, and control samples using data derived from serum protein profiling was compromised by bias.
McLerran
Dale
D
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Grizzle
William E
WE
Feng
Ziding
Z
Bigbee
William L
WL
Banez
Lionel L
LL
Cazares
Lisa H
LH
Chan
Daniel W
DW
Diaz
Jose
J
Izbicka
Elzbieta
E
Kagan
Jacob
J
Malehorn
David E
DE
Malik
Gunjan
G
Oelschlager
Denise
D
Partin
Alan
A
Randolph
Timothy
T
Rosenzweig
Nicole
N
Srivastava
Shiv
S
Srivastava
Sudhir
S
Thompson
Ian M
IM
Thornquist
Mark
M
Troyer
Dean
D
Yasui
Yutaka
Y
Zhang
Zhen
Z
Zhu
Liu
L
Semmes
O John
OJ
D000465:Algorithms; D015982:Bias; D014408:Biomarkers, Tumor / Q000097:blood*; D001800:Blood Specimen Collection; D003661:Decision Support Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D040901:Proteomics; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor