High-Purity CTC RNA Sequencing Identifies Prostate Cancer Lineage Phenotypes Prognostic for Clinical Outcomes
(2025) In Cancer Discovery 15(5). p.969-987- Abstract
The development of treatment resistance remains universal for patients with metastatic prostate cancer, driven by androgen receptor alterations and lineage state transitions. Identifying the evolution of lineage transitions in treatment resistance has been limited by the challenges of collecting serial tissue biopsies on treatment, which can be overcome using blood-based liquid biopsies. Using a novel circulating tumor cell (CTC) isolation approach, we collected 273 CTC samples from 117 patients with metastatic prostate cancer for RNA sequencing. One hundred forty-six samples from 70 patients had tumor purity comparable with tissue biopsies. We identified four CTC transcriptional phenotypes, mirroring lineage states identified in the... (More)
The development of treatment resistance remains universal for patients with metastatic prostate cancer, driven by androgen receptor alterations and lineage state transitions. Identifying the evolution of lineage transitions in treatment resistance has been limited by the challenges of collecting serial tissue biopsies on treatment, which can be overcome using blood-based liquid biopsies. Using a novel circulating tumor cell (CTC) isolation approach, we collected 273 CTC samples from 117 patients with metastatic prostate cancer for RNA sequencing. One hundred forty-six samples from 70 patients had tumor purity comparable with tissue biopsies. We identified four CTC transcriptional phenotypes, mirroring lineage states identified in the tissue. Patients with a luminal-B–like CTC phenotype defined by persistent androgen receptor signaling and high proliferation, as well as those with a neuroendocrine CTC phenotype, had significantly shorter survival than patients with luminal-A–like and low proliferation phenotypes. In a prospective substudy, pretreatment CTC luminal-B–like phenotype was associated with early progression on177 Lu–PSMA-617. Significance: Treatment resistance remains a universal driver of lethal metastatic prostate cancer, associated with acquired genomic alterations and lineage transitions. Using a novel high-purity CTC isolation approach for CTC transcriptional profiling, we identified four lineage phenotypes differentially associated with prognosis in metastatic prostate cancer.
(Less)
- author
- organization
- publishing date
- 2025-05-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Discovery
- volume
- 15
- issue
- 5
- pages
- 19 pages
- publisher
- American Association for Cancer Research Inc.
- external identifiers
-
- scopus:105005072636
- pmid:39912912
- ISSN
- 2159-8274
- DOI
- 10.1158/2159-8290.CD-24-1509
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Authors; Published by the American Association for Cancer Research.
- id
- f0223e20-f244-4b9f-8dad-ac78666d0577
- date added to LUP
- 2025-08-06 10:11:08
- date last changed
- 2025-08-20 11:27:02
@article{f0223e20-f244-4b9f-8dad-ac78666d0577,
abstract = {{<p>The development of treatment resistance remains universal for patients with metastatic prostate cancer, driven by androgen receptor alterations and lineage state transitions. Identifying the evolution of lineage transitions in treatment resistance has been limited by the challenges of collecting serial tissue biopsies on treatment, which can be overcome using blood-based liquid biopsies. Using a novel circulating tumor cell (CTC) isolation approach, we collected 273 CTC samples from 117 patients with metastatic prostate cancer for RNA sequencing. One hundred forty-six samples from 70 patients had tumor purity comparable with tissue biopsies. We identified four CTC transcriptional phenotypes, mirroring lineage states identified in the tissue. Patients with a luminal-B–like CTC phenotype defined by persistent androgen receptor signaling and high proliferation, as well as those with a neuroendocrine CTC phenotype, had significantly shorter survival than patients with luminal-A–like and low proliferation phenotypes. In a prospective substudy, pretreatment CTC luminal-B–like phenotype was associated with early progression on<sup>177</sup> Lu–PSMA-617. Significance: Treatment resistance remains a universal driver of lethal metastatic prostate cancer, associated with acquired genomic alterations and lineage transitions. Using a novel high-purity CTC isolation approach for CTC transcriptional profiling, we identified four lineage phenotypes differentially associated with prognosis in metastatic prostate cancer.</p>}},
author = {{Sharifi, Marina N. and Sperger, Jamie M. and Taylor, Amy K. and Tippins, Katharine E. and Reese, Shannon R. and Carreno, Viridiana and Kaufmann, Katherine R. and Chang, Alex H. and Nunamaker, Luke A. and Linebarger, Charlotte and Mora-Rodriguez, Leilani and Schehr, Jennifer L. and Krause, Hannah M. and Helzer, Kyle T. and Bootsma, Matthew L. and Blitzer, Grace C. and Floberg, John M. and Kyriakopoulos, Christos E. and Emamekhoo, Hamid and Heath, Elisabeth I. and Wells, Meghan and Tagawa, Scott T. and Sjöström, Martin and Choudhury, Atish D. and Yu, Menggang and Armstrong, Andrew J. and Rathkopf, Dana E. and Beltran, Himisha and Nelson, Peter S. and Feng, Felix Y. and Dehm, Scott M. and Kosoff, David and Wei, Xiao X. and McKay, Rana R. and Zhao, Shuang G. and Lang, Joshua M.}},
issn = {{2159-8274}},
language = {{eng}},
month = {{05}},
number = {{5}},
pages = {{969--987}},
publisher = {{American Association for Cancer Research Inc.}},
series = {{Cancer Discovery}},
title = {{High-Purity CTC RNA Sequencing Identifies Prostate Cancer Lineage Phenotypes Prognostic for Clinical Outcomes}},
url = {{http://dx.doi.org/10.1158/2159-8290.CD-24-1509}},
doi = {{10.1158/2159-8290.CD-24-1509}},
volume = {{15}},
year = {{2025}},
}