Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up
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RESEARCH ARTICLE
Open Access
Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up Heather Johnson1, Jinan Guo2,3, Xuhui Zhang4, Heqiu Zhang4, Athanasios Simoulis5, Alan H. B. Wu6, Taolin Xia7, Fei Li8, Wanlong Tan8, Allan Johnson9, Nishtman Dizeyi10, Per-Anders Abrahamsson10, Lukas Kenner11, Xiaoyan Feng4, Chang Zou3†, Kefeng Xiao2,3†, Jenny L. Persson12,13,14*† and Lingwu Chen15*†
Abstract Background: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. Methods: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRTPCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. Results: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963–0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929–0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956–0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980–0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947–0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. (Continued on next page)
* Correspondence: [email protected]; [email protected] † Chang Zou, Kefeng Xiao, Jenny L. Persson, and Lingwu Chen contributed equally as senior authors. 12 Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden 15 Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long
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