Evidence map›Paper›PMID 42183352›Full record

ArticleResearch square2026

Defining the combinatorial nature of gene modules in prostate cancer underlying lineage plasticity and metastasis.

Hanbing Song, Junxiang Xu, Keila Velazquez-Arcelay, Arda Demirci, Brendan L Raizenne, Sarah C Hsu, Joshua Choi, Julia H Pham, Yih-An Chen, Hannah N W Weinstein and 12 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Hanbing SongDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Junxiang XuDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Keila Velazquez-ArcelayDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Arda DemirciDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Brendan L RaizenneDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA.
Sarah C HsuDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Joshua ChoiDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Julia H PhamDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Yih-An ChenDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Hannah N W WeinsteinDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Isaac SalzmanDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Margaret TsuiDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Jon AkutagawaDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Wisdom AdingoDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Ezequiel GoldschmidtDepartment of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA.
Peter R CarrollDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA.
Julian C HongDepartment of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA.
Christopher M HeaphyDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Matthew R CooperbergDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA.
Nancy GreenlandDepartment of Pathology, University of California, San Francisco, San Francisco, CA USA.
Joshua D CampbellDepartment of Medicine, Boston University School of Medicine, Boston, Massachusetts.ORCID 0000-0003-0780-8662
Franklin W HuangDivision of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, Bakar Computational Health Sciences Institute, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.

Funding

Project 3: Understanding genomic and social and structural drivers of response-predictive inflammatory states underlying health disparities in patients with breast cancerU54CA302452 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Shawn L. Hervey-Jumper · 2025 to 2026
$7.3M
Investigating the mechanisms of driver genes associated with ancestry and aggressiveness in prostate cancerR01CA248920 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Joshua D Campbell · 2021 to 2026
$2.9M
NCI NIH HHS R01 CA248920NCI NIH HHS U54 CA302452
6 · The paper itself

Abstract

Prostate cancer encompasses a spectrum of disease states driven by complex cellular heterogeneity. To delineate the transcriptional programs underlying lineage plasticity and metastasis, we constructed a comprehensive single-cell atlas of 128 patients, spanning localized, castration-resistant, and metastatic disease. Lineage plasticity was prevalent in localized disease, with subsets of tumor cells adopting distinct basal-like and club-like states. Luminal-like cancer cells also displayed extensive lineage infidelity, defined not by a binary loss of identity but by the combinatorial erosion of luminal gene modules associated with higher grade and stage. In the metastatic setting, gene program association analysis (GPAS) identified a broad induction of cell-cycle gene modules across organ sites as well as an induction of organ-specific gene modules, including osteomimetic signaling in bone, neuro-migratory genes in brain, and erythroid-like transitions in liver. Neuroendocrine prostate cancers (NEPCs) were not monolithic but defined by combinations of NE-associated gene modules including a novel HES6 program. Notably, these modules were detected at intermediate levels in localized samples, suggesting molecular plasticity precedes histological transformation. We also developed a refined NE signature that could distinguish NEPC tumors more accurately than previously published signatures. Within the tumor microenvironment (TME), we observed an elevation of pro-inflammatory Th17 T-cells in African American patients and identified a rare Schwann cell population. Finally, we present PCformer, a transformer-based foundation model trained on >500,000 cells to automate cell-state classification. Together, this comprehensive atlas demonstrates the complex nature of gene modules underlying lineage infidelity and plasticity in cancer cells and highlights distinct immune and stromal populations within the tumor ecosystem.

Identifiers

PMID42183352
PMCPMC13193120

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.