EAU 2017: Identification of a CTC-based prognostic signature in mCRPC driven by Aurora Kinase A and Wnt signaling Identification of a CTC-based prognostic signature in mCRPC driven by Aurora Kinase A and Wnt signaling
CTCs were isolated from 5 mL whole blood using anti-EpCAM-conjugated magnetic beads. Following cell lysis, mRNA from CTCs was purified, followed by reverse transcription. Libraries were generated and qPCR was performed to evaluate a panel of 96 genes. Blood from 39 healthy controls was used as a referent. Gene expression data from prostate cancer cells (VCaP, PC3, and LNCaP) spiked into normal control blood was used for assay development, and CTCs from 43 patients with mCRPC were subsequently evaluated.
The Halabi nomogram[1], which predicts overall survival (OS) in mCRPC patients, was utilized to account for baseline clinicopathologic variables (opioid analgesic use, disease site, ECOG performance score, albumin, hemoglobin, alkaline phosphatase, and PSA). Cox regression multivariate analysis was used to identify genes independently associated with OS, and receiver operator curves were constructed to assess model performance.
Of 43 patients with mCRPC, 27 patients (63%) were identified with detectable CTCs, of which 21 deaths had occurred to date. Strong association with OS was demonstrated with the Halabi nomogram (HR 1.74, 95% CI 1.20-2.54), AURKA (HR 3.40, 95%CI 1.47-7.85), WNT5A (HR 2.71, 95%CI 1.43-5.13), and BMP7 (HR 2.10, 95%CI 1.25-3.52). A model including the Halabi nomogram, AURKA, BMP7, and WNT5A expression had an area under the curve (AUC) of 0.92 for predicting OS at 6 months in comparison with an AUC of 0.74 for the Halabi nomogram alone. This model was used to derive a CTC prognostic score, termed the miCTC score, ranging from 0-4 and incorporating AURKA, WNT5A gene expression along with the Halabi nomogram score.
In conclusion, this trial supports the ability to obtain valid expression profiles from small numbers of cells in the blood of mCRPC patients. This enables the assessment of target genes and has utility in predicting clinical outcomes in patients with aggressive prostate cancer.
[1] Halabi S1, Lin CY, Kelly WK, et al. Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2014 Mar 1;32(7):671-7
Speaker(s): Morgan T., Singhal U., Wang Y., Henderson J., Niknafs Y., Qiao Y., Taichman R., Zaslavsky A., Feng F., Palapattu G., Chinnaiyan A., Tomlins S.
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto
Twitter: @GoldbergHanan
at the #EAU17 - March 24-28, 2017- London, England