Patterns of intra- and intertumor phenotypic heterogeneity in lethal prostate cancer Journal Article
| Authors: | Roudier, M. P.; Gulati, R.; Sayar, E.; Patel, R. A.; Tratt, M.; Richards, H. M.; Cejas, P.; Munoz-Gomez, M.; Qiu, X.; Xie, Y.; Hanratty, B.; Zaidi, S.; Zhao, J. L.; Adil, M.; Mittal, C.; Zhao, Y.; Dumpit, R.; Coleman, I.; Low, J. Y.; Persse, T.; Galipeau, P.; Lee, J. K.; Tretiakova, M.; Chambers, M.; Vakar-Lopez, F.; True, L. D.; Perrone, M.; Lam, H. M.; Kollath, L. A.; Ding, C. C.; Harmon, S.; Cheng, H. H.; Yu, E. Y.; Montgomery, R. B.; Hawley, J. E.; Lin, D. W.; Corey, E.; Schweizer, M. T.; Setty, M.; Ha, G.; Sawyers, C. L.; Morrissey, C.; Long, H.; Nelson, P. S.; Haffner, M. C. |
| Article Title: | Patterns of intra- and intertumor phenotypic heterogeneity in lethal prostate cancer |
| Abstract: | Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intratumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 patients with mPC. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intrapatient intertumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | adult; controlled study; human tissue; protein expression; aged; middle aged; major clinical study; genetics; clinical feature; bone metastasis; cancer patient; lymph node metastasis; cell proliferation; prostate specific antigen; phenotype; metabolism; metastasis; cohort analysis; pathology; cell population; prostate cancer; prostatic neoplasms; liver metastasis; prostate tumor; neoplasm metastasis; genomics; metastasis potential; tissue microarray; androgen deprivation therapy; loss of function mutation; transcription factor sox2; genetic heterogeneity; synaptophysin; copy number variation; hepatocyte nuclear factor 3beta; single cell analysis; single-cell analysis; transcription factor mash1; cell proliferation rate; metastatic prostate cancer; gain of function mutation; time interval; clinical significance; humans; human; male; article; whole exome sequencing; knowledge gap; genetic profile; protein expression level; dispersity; single cell rna seq; tumor number; anatomical location; metastasis site |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 135 |
| Issue: | 15 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2025-08-01 |
| Start Page: | e186599 |
| Language: | English |
| DOI: | 10.1172/jci186599 |
| PUBMED: | 40493417 |
| PROVIDER: | scopus |
| PMCID: | PMC12321404 |
| DOI/URL: | |
| Notes: | Source: Scopus |
