PURPOSE: The pathological state of the prostate may be reflected by serum proteome in a man. We hypothesized that biomarkers are present in preoperative serum, which may be used to predict the probability of biochemical recurrence following radical prostatectomy. MATERIALS AND METHODS: Mass spectrometry analysis was used to compare 52 men who experienced biochemical recurrence with 52 who remained biochemical recurrence-free for approximately 5 years after radical retropubic prostatectomy. A total of 30 matched pairs of recurrent and nonrecurrent serum samples were randomly selected as a training set for biomarker discovery and model development. Selected mass spectrometry peaks were combined with pre-radical retropubic prostatectomy prostate specific antigen in a multivariate algorithm to predict recurrence. The algorithm was evaluated using the remaining 22 recurrent and 22 nonrecurrent subjects as test samples. Protein identities of the selected mass spectrometry peaks were investigated. RESULTS: Two serum biomarkers for recurrence, P1 and P2, were combined with preoperative prostate specific antigen to predict biochemical recurrence. The ROC AUC for prostate specific antigen and the predicted outcome was 0.606 and 0.691 in the testing data, respectively. Using a single cutoff the samples were divided into 2 groups that were predictive of biochemical recurrence (p = 0.026). In contrast, preoperative prostate specific antigen did not differ between recurrent and nonrecurrent cases (Wilcoxon matched pairs test p = 0.07). The protein identity of P1 was determined to be a truncated form of C4a (C4a des-Arg). Preliminary data indicated that P2 was an N-terminal fragment of protein C inhibitor. CONCLUSIONS: In the current study population, which was matched on Gleason score and TNM staging, pre-radical retropubic prostatectomy prostate specific antigen retained no independent power to predict recurrence. However, by adding 2 proteomic biomarkers to preoperative prostate specific antigen the combined model demonstrated statistically significant value for predicting prostate cancer recurrence in men who underwent radical retropubic prostatectomy.
PURPOSE: The pathological state of the prostate may be reflected by serum proteome in a man. We hypothesized that biomarkers are present in preoperative serum, which may be used to predict the probability of biochemical recurrence following radical prostatectomy. MATERIALS AND METHODS: Mass spectrometry analysis was used to compare 52 men who experienced biochemical recurrence with 52 who remained biochemical recurrence-free for approximately 5 years after radical retropubic prostatectomy. A total of 30 matched pairs of recurrent and nonrecurrent serum samples were randomly selected as a training set for biomarker discovery and model development. Selected mass spectrometry peaks were combined with pre-radical retropubic prostatectomy prostate specific antigen in a multivariate algorithm to predict recurrence. The algorithm was evaluated using the remaining 22 recurrent and 22 nonrecurrent subjects as test samples. Protein identities of the selected mass spectrometry peaks were investigated. RESULTS: Two serum biomarkers for recurrence, P1 and P2, were combined with preoperative prostate specific antigen to predict biochemical recurrence. The ROC AUC for prostate specific antigen and the predicted outcome was 0.606 and 0.691 in the testing data, respectively. Using a single cutoff the samples were divided into 2 groups that were predictive of biochemical recurrence (p = 0.026). In contrast, preoperative prostate specific antigen did not differ between recurrent and nonrecurrent cases (Wilcoxon matched pairs test p = 0.07). The protein identity of P1 was determined to be a truncated form of C4a (C4ades-Arg). Preliminary data indicated that P2 was an N-terminal fragment of protein C inhibitor. CONCLUSIONS: In the current study population, which was matched on Gleason score and TNM staging, pre-radical retropubic prostatectomy prostate specific antigen retained no independent power to predict recurrence. However, by adding 2 proteomic biomarkers to preoperative prostate specific antigen the combined model demonstrated statistically significant value for predicting prostate cancer recurrence in men who underwent radical retropubic prostatectomy.
Authors: Yiing Lin; Peter S Goedegebuure; Marcus C B Tan; Julia Gross; James P Malone; Sheng Feng; Justin Larson; Chanpheng Phommaly; Kathryn Trinkaus; R Reid Townsend; David C Linehan Journal: J Proteome Res Date: 2006-09 Impact factor: 4.466
Authors: Josep Villanueva; David R Shaffer; John Philip; Carlos A Chaparro; Hediye Erdjument-Bromage; Adam B Olshen; Martin Fleisher; Hans Lilja; Edi Brogi; Jeff Boyd; Marta Sanchez-Carbayo; Eric C Holland; Carlos Cordon-Cardo; Howard I Scher; Paul Tempst Journal: J Clin Invest Date: 2006-01 Impact factor: 14.808
Authors: Alex J Rai; Craig A Gelfand; Bruce C Haywood; David J Warunek; Jizu Yi; Mark D Schuchard; Richard J Mehigh; Steven L Cockrill; Graham B I Scott; Harald Tammen; Peter Schulz-Knappe; David W Speicher; Frank Vitzthum; Brian B Haab; Gerard Siest; Daniel W Chan Journal: Proteomics Date: 2005-08 Impact factor: 3.984
Authors: A W Partin; M W Kattan; E N Subong; P C Walsh; K J Wojno; J E Oesterling; P T Scardino; J D Pearson Journal: JAMA Date: 1997-05-14 Impact factor: 56.272
Authors: Ishtiaq Rehman; Caroline A Evans; Adam Glen; Simon S Cross; Colby L Eaton; Jenny Down; Giancarlo Pesce; Joshua T Phillips; Ow Saw Yen; George N Thalmann; Phillip C Wright; Freddie C Hamdy Journal: PLoS One Date: 2012-02-15 Impact factor: 3.240