J L García1, R Lozano2, I Misiewicz-Krzeminska3, J Fernández-Mateos2, P Krzeminski3, S Alfonso2, R A Marcos4, R García2, F Gómez-Veiga5, Á Virseda5, M Herrero5, D Olmos6,7, J J Cruz-Hernández8. 1. Institute of Biomedical Research of Salamanca (IBSAL), Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. jlgarcia@usal.es. 2. Medical Oncology Service, Hospital Universitario de Salamanca Institute of Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. 3. Institute of Biomedical Research of Salamanca (IBSAL), Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. 4. Dpto. de Oncología Médica, Complejo Asistencial Nuestra Señora de Sonsoles, Av.Juan Carlos I, s/n, 05071, Ávila, Spain. 5. Urology Department, Hospital Universitario de Salamanca Grupo de Investigación Traslacional de Urología (GITUR), Institute of Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. 6. Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain. 7. Medical Oncology Department, CNIO-IBIMA Genitourinary Cancer Clinical Research Unit, Hospital Universitario Virgen de la Victoria y Regional de Málaga, Campus de Teatinos S/N, 29010, Málaga, Spain. 8. Medical Oncology Service, Hospital Universitario de Salamanca Institute of Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. jjcruz@usal.es.
Abstract
PURPOSE: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform. Correlation with clinical data, stem cell biomarkers (such as CD133+), AR amplification and PTEN status was identified. RESULTS: The study included 72 PC patients. AR-V7 signal was detected in 21 (29%) patients: 17 (81%) had a Gleason score ≥7, 15 (71%) castration-resistant prostate cancer (CRPC), 18 (86%) metastatic disease and PSA (median) high than AR-V7 negative (p < 0.05). CD133 was expressed in 69 (96%) patients. The median CD133+ expression in circulating tumor cells CTCs was higher among the 21 AR-V7 positive cases versus AR-V7 negative (7 vs. 3). Androgen Receptor and PTEN fluorescence in situ hybridization (FISH) on CD133+ captured cells were performed: 37 cases showed ≥four CD133+ CTCs, of which 81% showed an increased AR copy number. This percentage was similar in both AR-V7-positive and AR-V7-negative patients. A total of 68% of the cases showed deletion of PTEN: 70% were ARV-7 positive vs. 67%, which were AR-V7 negative. CONCLUSIONS: Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 29% of the tumors and is more frequent in aggressive tumors.
PURPOSE:Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS:Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform. Correlation with clinical data, stem cell biomarkers (such as CD133+), AR amplification and PTEN status was identified. RESULTS: The study included 72 PC patients. AR-V7 signal was detected in 21 (29%) patients: 17 (81%) had a Gleason score ≥7, 15 (71%) castration-resistant prostate cancer (CRPC), 18 (86%) metastatic disease and PSA (median) high than AR-V7 negative (p < 0.05). CD133 was expressed in 69 (96%) patients. The median CD133+ expression in circulating tumor cells CTCs was higher among the 21 AR-V7 positive cases versus AR-V7 negative (7 vs. 3). Androgen Receptor and PTEN fluorescence in situ hybridization (FISH) on CD133+ captured cells were performed: 37 cases showed ≥four CD133+ CTCs, of which 81% showed an increased AR copy number. This percentage was similar in both AR-V7-positive and AR-V7-negative patients. A total of 68% of the cases showed deletion of PTEN: 70% were ARV-7 positive vs. 67%, which were AR-V7 negative. CONCLUSIONS: Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 29% of the tumors and is more frequent in aggressive tumors.
Authors: Shihua Sun; Cynthia C T Sprenger; Robert L Vessella; Kathleen Haugk; Kathryn Soriano; Elahe A Mostaghel; Stephanie T Page; Ilsa M Coleman; Holly M Nguyen; Huiying Sun; Peter S Nelson; Stephen R Plymate Journal: J Clin Invest Date: 2010-07-19 Impact factor: 14.808
Authors: Matias Knuuttila; Emrah Yatkin; Jenny Kallio; Saija Savolainen; Teemu D Laajala; Tero Aittokallio; Riikka Oksala; Merja Häkkinen; Pekka Keski-Rahkonen; Seppo Auriola; Matti Poutanen; Sari Mäkelä Journal: Am J Pathol Date: 2014-06-17 Impact factor: 4.307
Authors: Xiaotun Zhang; Colm Morrissey; Shihua Sun; Melanie Ketchandji; Peter S Nelson; Lawrence D True; Funda Vakar-Lopez; Robert L Vessella; Stephen R Plymate Journal: PLoS One Date: 2011-11-17 Impact factor: 3.240
Authors: Elizabeth A Punnoose; Roberta Ferraldeschi; Edith Szafer-Glusman; Eric K Tucker; Sankar Mohan; Penelope Flohr; Ruth Riisnaes; Susana Miranda; Ines Figueiredo; Daniel Nava Rodrigues; Aurelius Omlin; Carmel Pezaro; Jin Zhu; Lukas Amler; Premal Patel; Yibing Yan; Natalee Bales; Shannon L Werner; Jessica Louw; Ajay Pandita; Dena Marrinucci; Gerhardt Attard; Johann de Bono Journal: Br J Cancer Date: 2015-09-17 Impact factor: 7.640
Authors: Johann S de Bono; Howard I Scher; R Bruce Montgomery; Christopher Parker; M Craig Miller; Henk Tissing; Gerald V Doyle; Leon W W M Terstappen; Kenneth J Pienta; Derek Raghavan Journal: Clin Cancer Res Date: 2008-10-01 Impact factor: 12.531
Authors: Howard I Scher; David Lu; Nicole A Schreiber; Jessica Louw; Ryon P Graf; Hebert A Vargas; Ann Johnson; Adam Jendrisak; Richard Bambury; Daniel Danila; Brigit McLaughlin; Justin Wahl; Stephanie B Greene; Glenn Heller; Dena Marrinucci; Martin Fleisher; Ryan Dittamore Journal: JAMA Oncol Date: 2016-11-01 Impact factor: 31.777
Authors: Diego Fernández-Lázaro; Juan Luis García Hernández; Alberto Caballero García; Alfredo Córdova Martínez; Juan Mielgo-Ayuso; Juan Jesús Cruz-Hernández Journal: Diagnostics (Basel) Date: 2020-04-13