Cited 1 times since 2025 (1.9 per year) source: EuropePMC Cancer discovery, 6 1 2025 High-purity CTC RNA sequencing identifies prostate cancer lineage phenotypes prognostic for clinical outcomes. Sharifi MN, Sperger JM, Taylor AK, Tippins KE, Reese SR, Carreno V, Kaufmann KR, Chang AH, Nunamaker LA, Linebarger C, Mora-Rodriguez L, Schehr JL, Krause HM, Helzer KT, Bootsma ML, Blitzer GC, Floberg JM, Kyriakopoulos CE, Emamekhoo H, Heath EI, Wells M, Tagawa ST, Sjöström M, Choudhury AD, Yu M, Armstrong AJ, Rathkopf DE, Beltran H, Nelson PS, Feng FY, Dehm SM, Kosoff D, Wei XX, McKay RR, Zhao SG, Lang JM
The development of treatment resistance remains universal for patients with metastatic prostate cancer, driven by AR 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. Utilizing a novel circulating tumor cell (CTC) isolation approach, we collected 273 CTC samples from 117 patients with metastatic prostate cancer for RNA sequencing. 146 samples from 70 patients had tumor purity comparable to tissue biopsies. We identified four CTC transcriptional phenotypes, mirroring lineage states identified in tissue. Patients with a luminal-B-like CTC phenotype defined by persistent AR 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, pre-treatment CTC luminal-B-like phenotype was associated with early progression on 177Lu-PSMA-617.
