Dynamics of three-dimensional telomere profiles of circulating tumor cells in patients with high-risk prostate cancer who are undergoing androgen deprivation and radiation therapies

Urol Oncol. 2017 Mar;35(3):112.e1-112.e11. doi: 10.1016/j.urolonc.2016.10.018. Epub 2016 Dec 10.

Abstract

Introduction: Accurate assessment and monitoring of the therapeutic efficacy of locally advanced prostate cancer remains a major clinical challenge. Contrary to prostate biopsies, circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling and could serve as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate and enumerate CTCs from the blood of 20 patients with high-risk (any one of cT3, Gleason 8-10, or prostate-specific antigen>20ng/ml), nonmetastatic, and treatment-naive prostate cancer before and after androgen deprivation therapy (ADT) and radiation therapy (RT).

Materials and methods: We performed 3D telomere-specific quantitative fluorescence in situ hybridization on isolated CTCs to determine 3D telomere profiles for each patient before and throughout the course of both ADT and RT.

Results: Based on the distinct 3D telomere signatures of CTC before treatment, patients were divided into 3 groups. ADT and RT resulted in distinct changes in 3D telomere signatures of CTCs, which were unique for each of the 3 patient groups.

Conclusion: The ability of 3D telomere analysis of CTCs to identify disease heterogeneity among a clinically homogeneous group of patients, which reveals differences in therapeutic responses, provides a new opportunity for better treatment monitoring and management of patients with high-risk prostate cancer.

Keywords: Biomarkers; Circulating tumor cells; High-risk prostate cancer; Telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Cell Count / methods
  • Cell Nucleus / metabolism
  • Chemoradiotherapy / methods
  • Female
  • Genomic Instability / drug effects*
  • Genomic Instability / radiation effects
  • Healthy Volunteers
  • Humans
  • Imaging, Three-Dimensional / methods
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence / methods
  • Kallikreins / blood
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Neoplastic Cells, Circulating / drug effects*
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / radiation effects
  • Prostate / pathology
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Receptors, Androgen / metabolism
  • Telomere / drug effects*
  • Telomere / metabolism
  • Telomere / radiation effects
  • Telomere / ultrastructure
  • Treatment Outcome

Substances

  • AR protein, human
  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Receptors, Androgen
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen