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Multi-omic serum biomarkers for prognosis of disease progression in prostate cancer.
Kiebish, Michael A; Cullen, Jennifer; Mishra, Prachi; Ali, Amina; Milliman, Eric; Rodrigues, Leonardo O; Chen, Emily Y; Tolstikov, Vladimir; Zhang, Lixia; Panagopoulos, Kiki; Shah, Punit; Chen, Yongmei; Petrovics, Gyorgy; Rosner, Inger L; Sesterhenn, Isabell A; McLeod, David G; Granger, Elder; Sarangarajan, Rangaprasad; Akmaev, Viatcheslav; Srinivasan, Alagarsamy; Srivastava, Shiv; Narain, Niven R; Dobi, Albert.
Afiliación
  • Kiebish MA; BERG LLC, Framingham, MA, USA.
  • Cullen J; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Mishra P; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Ali A; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Milliman E; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Rodrigues LO; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Chen EY; BERG LLC, Framingham, MA, USA.
  • Tolstikov V; BERG LLC, Framingham, MA, USA.
  • Zhang L; BERG LLC, Framingham, MA, USA.
  • Panagopoulos K; BERG LLC, Framingham, MA, USA.
  • Shah P; BERG LLC, Framingham, MA, USA.
  • Chen Y; BERG LLC, Framingham, MA, USA.
  • Petrovics G; BERG LLC, Framingham, MA, USA.
  • Rosner IL; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Sesterhenn IA; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • McLeod DG; Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Granger E; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Sarangarajan R; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Akmaev V; Joint Pathology Center, Silver Spring, MD, USA.
  • Srinivasan A; Center for Prostate Disease Research, Department of Surgery, Uniformed Services University and the Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Srivastava S; BERG LLC, Framingham, MA, USA.
  • Narain NR; BERG LLC, Framingham, MA, USA.
  • Dobi A; BERG LLC, Framingham, MA, USA.
J Transl Med ; 18(1): 10, 2020 01 07.
Article en En | MEDLINE | ID: mdl-31910880
ABSTRACT

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) 180-220 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 reproduced an equivalent performance with high negative predictive value (NPV; > 80%) for BCR. The combination of pTstage and Gleason score with the analytes, further increased the sensitivity [AUC = 0.89, 95% (CI) = 4.45-32.05, P < 0.05], with an increased NPV (0.96) and OR (12.4) for BCR. The panel of markers combined with the pathological parameters demonstrated a more accurate prediction of BCR than the pathological parameters alone in prostate cancer.

CONCLUSIONS:

In this study, a panel of serum analytes were identified that complemented pathologic patient features in predicting prostate cancer progression. This panel offers a new opportunity to complement current prognostic markers and to monitor the potential impact of primary treatment versus surveillance on patient oncological outcome.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Prostatectomía / Neoplasias de la Próstata Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans / Male Idioma: En Revista: J Transl Med Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Prostatectomía / Neoplasias de la Próstata Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans / Male Idioma: En Revista: J Transl Med Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos