Abstract 3389: A multi-gene prostate cancer liquid biopsy with &amp;gt; 92% accuracy in diagnosis and assessment of disease status
Authors: Kambiz Rahbar, Mark Kidd, Ignat Drozdov, Alexandra Kitz, Anna Malczewska, Pawel Rajwa, Christof Bernemann, Lisa Bodei, Irvin Modlin
Journal: Cancer Research (2020)

Abstract Background: There are a paucity of blood-based biomarkers with clinical utility for prostate cancer (PCa). We examined a circulating-free mRNA (27-gene) prostate cancer signature to diagnose PCa. Clinical utility of the assay was then assessed in surgical patients. Methods: Gene identification and validation: Publicly available PCa transcriptome sets (n=5) (E-GEOD-46691, E-GEOD-46602, E-GEOD-62116, E-GEOD-62667, E-GEOD-72220: n=1,159 samples); PCA cell lines (n=7) gene expression in 22Rv1 and E006AA-hT (localized); VCaP; PC-3; LNCaP; DU145 and MDA PCa2b (all metastatic) from two normal prostate epithelial lines: PWR-1E and RWPE-1 and validated in PCa tumor tissue (n=50). Transcriptome analyses: tumor compared with normal blood-based transcriptomes using gene co-expression network enrichment, differential expression and functional enrichment analyses to identify candidate markers. Blood gene expression: PCa set #I: n=132, PCA set #II: n=50 (biochemical recurrence [BCR]), BPH: n=44, controls n=55. We then constructed an artificial intelligence PCa model using classification algorithm analyses. Scoring: normalized algorithmically analyzed gene expression (0 to 100), positive score ≥20. Matched tumor/ blood samples: n=50. PSA: BPH (n=44) and PCa (n=132). Clinical score assessment: Score utility was assessed in surgical cohorts: Surgical: (n=47), scores =pre-surgical and post: 1 week - 14 months. Statistics: Non-parametric (Kruskal-Wallis), Pearson-correlation, Fisher's and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis identified a 27 gene blood signature for PCa. Expression levels were significantly elevated (p&amp;lt;0.001, 2.1-35.8-fold) in cell lines and PCA tumors. The matched tissue/blood correlation was r: 0.56 (p=0.0023). In PCa #I, levels were 47±2 (p&amp;lt;0.0001) compared to BPH (19±1) and controls (18±0.5); AUROC: 0.92 (BPH) and 0.94 (controls), with an accuracy of 85-88%, a sensitivity of 86% and specificities 82 &amp; 93% respectively. For PSA the AUROC (PCa vs. BPH) was 0.51 (p=0.88). PSA was positive in 86% of BPH and was &amp;gt;10ng/ml in 30%. PSA was positive in 83% of PCa and &amp;gt;10ng/ml in 40% (Fisher's exact: p=0.28). PSA accuracy (&amp;gt;10ng/ml) was 48%. Levels in PCA #II (BCR) were 44±3. ProstaTest-was positive in 48 (96%). Surgical cohort (n=47): PCa Prostatest accuracy 100% pre-surgery. Resection significantly decreased levels (KW-statistic: 57.4, p&amp;lt;0.0001) from 52±1 to 23.5±2. Conclusion: The diagnostic accuracy of a PCa molecular blood-signature was 92%; significantly better than PSA (48%, p&amp;lt;0.0001). Surgical resection significantly (p&amp;lt;0.0001) decreased levels. Biochemical recurrence was accurately detected (96%). A multi-gene prostate cancer liquid biopsy seems likely to have clinical utility in the diagnosis and monitoring management of PCa. Citation Format: Kambiz Rahbar, Mark Kidd, Ignat Drozdov, Alexandra Kitz, Anna Malczewska, Pawel Rajwa, Christof Bernemann, Lisa Bodei, Irvin Modlin. A multi-gene prostate cancer liquid biopsy with &amp;gt; 92% accuracy in diagnosis and assessment of disease status [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 3389.