A novel methylated cell-free DNA marker panel to monitor treatment response in metastatic prostate cancer-Reference-Cited by-同舟云学术

A novel methylated cell-free DNA marker panel to monitor treatment response in metastatic prostate cancer

Published:2022-07 Issue:13 Volume:14 Page:811-822
ISSN:1750-1911
Container-title:Epigenomics
language:en
Short-container-title:Epigenomics

Author:

Peter Madonna R¹²,Bilenky Misha³,Shi Yuliang⁴,Pu Jiajie⁴,Kamdar Shivani¹²,Hansen Aaron R⁵,Fleshner Neil E⁶,Sridhar Srikala S⁵,Joshua Anthony M⁵⁷,Hirst Martin³⁸^ORCID,Xu Wei⁴,Bapat Bharati¹²

Affiliation:

1. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada

2. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada

3. Canada's Michael Smith Genome Science Center, BC Cancer Agency, Vancouver, BC, V5Z 4S6, Canada

4. Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 2C1, Canada

5. Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, M5G 2C1, Canada

6. Division of Urology, Department of Surgical Oncology, University Health Network, Toronto, ON, M5G 2C1, Canada

7. Department of Medical Oncology, Kinghorn Cancer Centre, Darlinghurst, NSW 2010, Australia

8. Department of Microbiology & Immunology & Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada

Abstract

Aim: This study examined circulating cell-free DNA (cfDNA) biomarkers associated with androgen treatment resistance in metastatic castration resistance prostate cancer (mCRPC). Materials & methods: We designed a panel of nine candidate cfDNA methylation markers using droplet digital PCR (Methyl-ddPCR) and assessed methylation levels in sequentially collected cfDNA samples from patients with mCRPC. Results: Increased cfDNA methylation in eight out of nine markers during androgen-targeted treatment correlated with a faster time to clinical progression. Cox proportional hazards modeling and logistic regression analysis further confirmed that higher cfDNA methylation during treatment was significantly associated with clinical progression. Conclusion: Overall, our findings have revealed a novel methylated cfDNA marker panel that could aid in the clinical management of metastatic prostate cancer.

Funder

Prostate Cancer Canada Movember Discovery Grant

CUA-CUOG-Astellas Research Grant

Astellas Prostate Cancer Innovation Fund

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

Link

https://www.futuremedicine.com/doi/pdf/10.2217/epi-2022-0103

Reference35 articles.

1. Prostate cancer