A four-gene transcript score to predict metastatic-lethal progression in men treated for localized prostate cancer: development and validation studies
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.
Publication titleThe Prostate
Department/SchoolMenzies Institute for Medical Research
Place of publicationDiv John Wiley & Sons Inc, 605 Third Ave, New York, USA, Ny, 10158-0012
Rights statement© 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: