Abstract 1999: Diagnostic utility of the NETest in neuroendocrine transformed prostate cancer

Published on Aug 15, 2020in Cancer Research9.727
· DOI :10.1158/1538-7445.AM2020-1999
Kambiz Rahbar22
Estimated H-index: 22
Mark Kidd66
Estimated H-index: 66
+ 6 AuthorsIrvin M. Modlin81
Estimated H-index: 81
(Yale University)
Background: Neuroendocrine differentiation and the development of an aggressive phenotype are key features of castration-resistant prostate cancer (CRPC) disease. Current blood-based biomarkers cannot detect these treatment-refractory cancer variants. Aims: Evaluate the utility of the NETest, a blood-based 51-marker gene neuroendocrine detection tool, as a CRPC diagnostic and examine which functional gene clusters (hallmarks) differentiate CRPC from PCa. Methods:NETest gene identification in CRPC: Publicly available CRPC RNAseq dataset (cBIO Portal: dbGap phs000909.v.p1, tissue samples: n=47, including 15 neuroendocrine CRPC). Blood gene expression: Prostate cancers (PCa): (n=50) CRPC, (n=40) hormone-sensitive PCa (n=75), and benign prostatic hyperplasia (BPH) (n=41). NETest assay: PCR (51 genes): Expression normalized and categorized into functional classifiers. 51 markers algorithmically assessed and scored: 0-100. Cut-off 40 for progressive disease. PSA: ECLIA diagnostic assay: cut-off 4ng/L, >10ng/ml=critical value. Statistics: ANOVA, AUROC analyses and sensitivity/specificity metrics. Data is mean±SEM. Results:RNA tissue seq: Captured all 51 NETest genes (100%). Thirty-three (65%) genes were detected as upregulated in CRPC tumors (1.09-1425 fold elevated over normal tissue). Blood-PCR: In CRPC, detected in 49/51 (96%) NETest genes. Gene expression was significantly upregulated (p 10ng/ml occurred in 63% of CRPC, 55% of PCA (p=NS) and 24% of BPH (p Conclusion: The NETest detects neuroendocrine neoplasia genes in the blood and accurately identifies genomic hallmarks of castration-resistant prostate cancer. It performs significantly better than PSA. This multi-gene NETest liquid biopsy is likely to have clinical utility in the diagnosis of CRPC and provide a basis to stratify patients for CRPC-based therapies. Citation Format: Kambiz Rahbar, Mark Kidd, Ignat Drozdov, Alexandra Kitz, Anna Malczewska, Lisa Bodei, Pawel Rajwa, Christof Bernemann, Irvin Modlin. Diagnostic utility of the NETest in neuroendocrine transformed prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1999.
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