Multi-omic serum biomarkers for prognosis of disease progression in prostate cancer

作者：Michael A. Kiebish, Jennifer Cullen, Prachi Mishra, Amina Ali, Eric Milliman, Leonardo O. Rodrigues, Emily Y. Chen, Vladimir Tolstikov, Lixia Zhang, Kiki Panagopoulos, Punit Shah, Yongmei Chen, György Petrovics, Inger L. Rosner, Isabell A. Sesterhenn, David G. McLeod, Elder Granger, Rangaprasad Sarangarajan, Viatcheslav R. Akmaev, Alagarsamy Srinivasan, Shiv Srivastava, Niven R. Narain, Albert Dobi · 发表于：Journal of Translational Medicine · 年份：2020 · DOI：10.1186/s12967-019-02185-y · 被引用次数：69 · 研究领域：Ferroptosis and cancer prognosis、Clusterin in disease pathology、Prostate Cancer Diagnosis and Treatment

BACKGROUND: Predicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The objective of our study was to identify prostate cancer prognostic markers in patients 'sera using a multi-omics discovery platform. METHODS: Pre-surgical serum samples collected from a longitudinal, racially diverse, prostate cancer patient cohort (N = 382) were examined. Linear Regression and Bayesian computational approaches integrated with multi-omics, were used to select markers to predict biochemical recurrence (BCR). BCR-free survival was modeled using unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis, adjusted for key pathologic variables. Receiver operating characteristic (ROC) curve statistics were used to examine the predictive value of markers in discriminating BCR events from non-events. The findings were further validated by creating a training set (N = 267) and testing set (N = 115) from the cohort. RESULTS: Among 382 patients, 72 (19%) experienced a BCR event in a median follow-up time of 6.9 years. Two proteins-Tenascin C (TNC) and Apolipoprotein A1V (Apo-AIV), one metabolite-1-Methyladenosine (1-MA) and one phospholipid molecular species phosphatidic acid (PA) 18:0-22:0 showed a cumulative predictive performance of AUC = 0.78 [OR (95% CI) = 6.56 (2.98-14.40), P < 0.05], in differentiating patients with and without BCR event. In the validation set all four metabolites consistently repro...