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A clinical-grade liquid biomarker detects neuroendocrine differentiation in prostate cancer

The Journal of clinical investigation, 2022-11, Vol.132 (21) [Peer Reviewed Journal]

COPYRIGHT 2022 American Society for Clinical Investigation ;2022 Zhao et al. 2022 Zhao et al. ;ISSN: 1558-8238 ;ISSN: 0021-9738 ;EISSN: 1558-8238 ;DOI: 10.1172/JCI161858 ;PMID: 36317634

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Title:
A clinical-grade liquid biomarker detects neuroendocrine differentiation in prostate cancer
Author: Zhao, Shuang G ; Sperger, Jamie M ; Schehr, Jennifer L ; McKay, Rana R ; Emamekhoo, Hamid ; Singh, Anupama ; Schultz, Zachery D ; Bade, Rory M ; Stahlfeld, Charlotte N ; Gilsdorf, Cole S ; Hernandez, Camila I ; Wolfe, Serena K ; Mayberry, Richel D ; Krause, Hannah M ; Bootsma, Matt ; Helzer, Kyle T ; Rydzewski, Nicholas ; Bakhtiar, Hamza ; Shi, Yue ; Blitzer, Grace ; Kyriakopoulos, Christos E ; Kosoff, David ; Wei, Xiao X ; Floberg, John ; Sethakorn, Nan ; Sharifi, Marina ; Harari, Paul M ; Huang, Wei ; Beltran, Himisha ; Choueiri, Toni K ; Scher, Howard I ; Rathkopf, Dana E ; Halabi, Susan ; Armstrong, Andrew J ; Beebe, David J ; Yu, Menggang ; Sundling, Kaitlin E ; Taplin, Mary-Ellen ; Lang, Joshua M
Subjects: Adenocarcinoma - diagnosis ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Biomarkers ; Cell Line, Tumor ; Clinical Medicine ; Development and progression ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Health aspects ; Humans ; Male ; Medical research ; Medicine, Experimental ; Metastasis ; Oncology ; Prognosis ; Prostate cancer ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Receptors, Androgen - genetics ; Receptors, Androgen - metabolism ; RNA ; Signal Transduction ; Tumor markers
Is Part Of: The Journal of clinical investigation, 2022-11, Vol.132 (21)
Description: BackgroundNeuroendocrine prostate cancer (NEPC) is an aggressive subtype, the presence of which changes the prognosis and management of metastatic prostate cancer.MethodsWe performed analytical validation of a Circulating Tumor Cell (CTC) multiplex RNA qPCR assay to identify the limit of quantification (LOQ) in cell lines, synthetic cDNA, and patient samples. We next profiled 116 longitudinal samples from a prospectively collected institutional cohort of 17 patients with metastatic prostate cancer (7 NEPC, 10 adenocarcinoma) as well as 265 samples from 139 patients enrolled in 3 adenocarcinoma phase II trials of androgen receptor signaling inhibitors (ARSIs). We assessed a NEPC liquid biomarker via the presence of neuroendocrine markers and the absence of androgen receptor (AR) target genes.ResultsUsing the analytical validation LOQ, liquid biomarker NEPC detection in the longitudinal cohort had a per-sample sensitivity of 51.35% and a specificity of 91.14%. However, when we incorporated the serial information from multiple liquid biopsies per patient, a unique aspect of this study, the per-patient predictions were 100% accurate, with a receiver-operating-curve (ROC) AUC of 1. In the adenocarcinoma ARSI trials, the presence of neuroendocrine markers, even while AR target gene expression was retained, was a strong negative prognostic factor.ConclusionOur analytically validated CTC biomarker can detect NEPC with high diagnostic accuracy when leveraging serial samples that are only feasible using liquid biopsies. Patients with expression of NE genes while retaining AR-target gene expression may indicate the transition to neuroendocrine differentiation, with clinical characteristics consistent with this phenotype.FundingNIH (DP2 OD030734, 1UH2CA260389, R01CA247479, and P30 CA014520), Department of Defense (PC190039 and PC200334), and Prostate Cancer Foundation (Movember Foundation - PCF Challenge Award).
Publisher: United States: American Society for Clinical Investigation
Language: English
Identifier: ISSN: 1558-8238
ISSN: 0021-9738
EISSN: 1558-8238
DOI: 10.1172/JCI161858
PMID: 36317634
Source: Geneva Foundation Free Medical Journals at publisher websites
AUTh Library subscriptions: ProQuest Central
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PubMed Central
Alma/SFX Local Collection
DOAJ Directory of Open Access Journals

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A clinical-grade liquid biomarker detects neuroendocrine differentiation in prostate cancer

COPYRIGHT 2022 American Society for Clinical Investigation ;2022 Zhao et al. 2022 Zhao et al. ;ISSN: 1558-8238 ;ISSN: 0021-9738 ;EISSN: 1558-8238 ;DOI: 10.1172/JCI161858 ;PMID: 36317634

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