PD71-07 GAS6, KLK2, AND BMP7 DETECTED IN CIRCULATING TUMOR CELLS PREDICT RESISTANCE TO CHEMOTHERAPY IN MCRPC

Abstract

You have accessJournal of UrologyProstate Cancer: Markers III1 Apr 2017PD71-07 GAS6, KLK2, AND BMP7 DETECTED IN CIRCULATING TUMOR CELLS PREDICT RESISTANCE TO CHEMOTHERAPY IN MCRPC Jae-Seung Chung, Yugang Wang, Henderson James, Udit Singhal, Yuanyuan Qiao, Alexander Zaslavsky, Dan Hovelson, Felix Feng, Ganesh Palapattu, Taichman Russell, Arul Chinnaiyan, Scott Tomlins, and Todd Morgan Jae-Seung ChungJae-Seung Chung More articles by this author , Yugang WangYugang Wang More articles by this author , Henderson JamesHenderson James More articles by this author , Udit SinghalUdit Singhal More articles by this author , Yuanyuan QiaoYuanyuan Qiao More articles by this author , Alexander ZaslavskyAlexander Zaslavsky More articles by this author , Dan HovelsonDan Hovelson More articles by this author , Felix FengFelix Feng More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , Taichman RussellTaichman Russell More articles by this author , Arul ChinnaiyanArul Chinnaiyan More articles by this author , Scott TomlinsScott Tomlins More articles by this author , and Todd MorganTodd Morgan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3174AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Docetaxel or cabazitaxel-based chemotherapy continues to have a critical role in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). However, responses are heterogeneous and resistance to therapy is a pressing clinical problem. With the goal of developing liquid biomarkers to aid in treatment selection, we sought to identify genes associated with resistance to chemotherapy using a circulating tumor cell (CTC)-based approach. METHODS Whole blood (~5mL) was obtained from 25 patients with mCRPC starting docetaxel (n=21) or cabazitaxel (n=4). CTCs were isolated using anti-EpCAM-conjugated magnetic beads, and following cell lysis, mRNA was extracted followed by multiplex qRT-PCR for 44 prostate cancer-related genes plus internal controls. Gene expression was normalized to controls, and samples were considered CTC-positive based on a previously established set of epithelial markers (EpCAM, EGFR, DSG2, KRT8, KRT18 and KRT19). The primary endpoint was PSA progression-free survival (PFS), with PSA progression defined as an increase of 25% or more above the nadir. Univariable Cox regression analyses were performed to assess for genes associated with PFS at false discovery rate (FDR) < 0.20. RESULTS Among 25 patients with mCRPC, we identified 84% (21/25) with detectable CTCs. The median age of the cohort was 62 years (IQR 58-70). At a median (IQR) follow up of 5.4 (3.4-9.3) months, 47.6 % (10/21) of patients showed a PSA decrease of at least 30% following treatment initiation. 18/21 patients (85.7%) experienced PSA progression at a median of 2.8 months (IQR 1.7-4.8). In the Cox analysis, KLK2 (HR 2.54, 95%CI 1.24-5.21, p=0.011), GAS6 (HR 3.50, 95%CI 1.30-9.42, p=0.013), and BMP7 (HR 2.01, 95%CI 1.15-3.52; p=0.014) were associated with shorter PFS. CONCLUSIONS We have identified three genes associated with progression in mCRPC patients initiating chemotherapy. While these early results need further confirmation, they suggest that CTCs may be utilized to help guide precision-based treatment strategies in patients with mCRPC. Additionally, these results corroborate our recent in vitro and in vivo findings (Lee et al, J Cell Biochem, 2016) indicating that GAS6 protects prostate cancer cells from docetaxel-induced apoptosis. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1358 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jae-Seung Chung More articles by this author Yugang Wang More articles by this author Henderson James More articles by this author Udit Singhal More articles by this author Yuanyuan Qiao More articles by this author Alexander Zaslavsky More articles by this author Dan Hovelson More articles by this author Felix Feng More articles by this author Ganesh Palapattu More articles by this author Taichman Russell More articles by this author Arul Chinnaiyan More articles by this author Scott Tomlins More articles by this author Todd Morgan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...