Predicting Prostate Cancer Biochemical Recurrence Using a Panel of Serum Proteomic Biomarkers

C. Nicole Rosenzweig, Zhen Zhang, Xiaer Sun, Lori J Sokoll, Katherine Osborne, Alan Wayne Partin, Daniel Wan-Yui Chan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1407-1414
Number of pages8
JournalJournal of Urology
Volume181
Issue number3
DOIs
StatePublished - Mar 2009

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Proteomics
Prostatic Neoplasms
Biomarkers
Prostate-Specific Antigen
Recurrence
Prostatectomy
Serum
Mass Spectrometry
Protein C Inhibitor
Neoplasm Grading
Neoplasm Staging
Proteome
Area Under Curve
Prostate
Proteins
Population

Keywords

  • complement C4a
  • neoplasm recurrence
  • prostate
  • prostatic neoplasms
  • protein C inhibitor

ASJC Scopus subject areas

  • Urology

Cite this

Predicting Prostate Cancer Biochemical Recurrence Using a Panel of Serum Proteomic Biomarkers. / Rosenzweig, C. Nicole; Zhang, Zhen; Sun, Xiaer; Sokoll, Lori J; Osborne, Katherine; Partin, Alan Wayne; Chan, Daniel Wan-Yui.

In: Journal of Urology, Vol. 181, No. 3, 03.2009, p. 1407-1414.

Research output: Contribution to journalArticle

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abstract = "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.",
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