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Abstract

Background: Molecular studies have tried to address the unmet need for prognostic biomarkers in prostate cancer (PCa). Some gene expression tests improve upon clinical factors for prediction of outcomes, but additional tools for accurate prediction of tumor aggressiveness are needed.Methods: Based on a previously published panel of 23 gene transcripts that distinguished patients with metastatic progression, we constructed a prediction model using independent training and testing datasets. Using the validated messenger RNAs and Gleason score (GS), we performed model selection in the training set to define a final locked model to classify patients who developed metastatic-lethal events from those who remained recurrence-free. In an independent testing dataset, we compared our locked model to established clinical prognostic factors and utilized Kaplan-Meier curves and receiver operating characteristic analyses to evaluate the model's performance.Results: Thirteen of 23 previously identified gene transcripts that stratified patients with aggressive PCa were validated in the training dataset. These biomarkers plus GS were used to develop a four-gene (CST2, FBLN1, TNFRSF19, and ZNF704) transcript (4GT) score that was significantly higher in patients who progressed to metastatic-lethal events compared to those without recurrence in the testing dataset (P = 5.7 × 10-11). The 4GT score provided higher prediction accuracy (area under the ROC curve [AUC] = 0.76; 95% confidence interval [CI] = 0.69-0.83; partial area under the ROC curve [pAUC] = 0.008) than GS alone (AUC = 0.63; 95% CI = 0.56-0.70; pAUC = 0.002), and it improved risk stratification in subgroups defined by a combination of clinicopathological features (ie, Cancer of the Prostate Risk Assessment-Surgery).Conclusion: Our validated 4GT score has prognostic value for metastatic-lethal progression in men treated for localized PCa and warrants further evaluation for its clinical utility.

Item Type:	Article
Authors/Creators:	Cheng, A and Zhao, S and FitzGerald, LM and Wright, JL and Kolb, S and Karnes, RJ and Jenkins, RB and Davicioni, E and Ostrander, EA and Feng, Z and Fan, J-B and Dai, JY and Stanford, JL
Keywords:	biomarkers, metastatic-lethal, prognosis, prostate cancer, validation
Journal or Publication Title:	The Prostate
Publisher:	Wiley-Liss
ISSN:	0270-4137
DOI / ID Number:	https://doi.org/10.1002/pros.23882
Copyright Information:	© 2019 Wiley Periodicals. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This is the peer reviewed version of the following article: Cheng, A and Zhao, S and FitzGerald, LM and Wright, JL and Kolb, S and Karnes, RJ and Jenkins, RB and Davicioni, E and Ostrander, EA and Feng, Z and Fan, J-B and Dai, JY and Stanford, JL, A four-gene transcript score to predict metastatic-lethal progression in men treated for localized prostate cancer: Development and validation studies, The Prostate, 79, (14) pp. 1589-1596. ISSN 0270-4137 (2019), which has been published in final form at:
Related URLs:	Google Scholar: FitzGerald, LM
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