GEO series
A single-cell and spatial atlas of prostate cancer reveals the combinatorial nature of gene modules underlying lineage plasticity and metastasis
GSE324131
Homo sapiens
Expression profiling by high throughput sequencing
38 samples
Submitted 2026/05/01
Platform GPL34281
Summary
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.
Published in
Song H, Xu J, Velazquez-Arcelay K et al.
· Research square 2026
· PMID 42183352
· doi:10.21203/rs.3.rs-9430776/v1
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE324131_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 38 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1433496 and SRA study SRP681768. Searching any of these in the dataset finder brings you back here.
Study design
13 conditions, mostly in duplicate
Patient_PCa3_Tumor_Replica ×4
Patient_PCa6_Tumor_Replica ×4
Patient_PR5316_N_apex_V ×2
Patient_PR5316_N_base_V ×2
Patient_PR5316_T_apex_V ×2
Patient_PROS505-3_replicaA ×2
Patient_PROS505-3_replicaB ×2
Patient_PROS505-3_replicaC ×2
+13 more
Supports a between-group comparison across 30 samples.
13 replicated groups read from 38 sample titles; they account for 30 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9568704 Patient_PR5316_N_apex_V1
- GSM9568705 Patient_PR5316_N_apex_V2
- GSM9568706 Patient_PR5316_N_base_V1
- GSM9568707 Patient_PR5316_N_base_V2
- GSM9568708 Patient_PR5316_T_apex_V1
- GSM9568709 Patient_PR5316_T_apex_V2
- GSM9568710 Patient_PR5316_T_base_V1
- GSM9568711 Patient_PCA2_replicaA
- GSM9568712 Patient_PCA2_replicaB
- GSM9568713 Patient_PROS505-3_replicaA1
- GSM9568714 Patient_PROS505-3_replicaA2
- GSM9568715 Patient_PROS505-3_replicaB1
- GSM9568716 Patient_PROS505-3_replicaB2
- GSM9568717 Patient_PROS505-3_replicaC1
- GSM9568718 Patient_PROS505-3_replicaC2
- GSM9568719 Patient_PROS505-3_replicaD1
- GSM9568720 Patient_PROS505-3_replicaD2
- GSM9568721 Patient_VAPROS1-1_replicaA1
- GSM9568722 Patient_VAPROS1-1_replicaA2
- GSM9568723 Patient_VAPROS1-1_replicaB1
- GSM9568724 Patient_VAPROS1-1_replicaB2
- GSM9568725 Patient_VAPROS1-1_replicaC1
- GSM9568726 Patient_VAPROS1-1_replicaC2
- GSM9568727 Patient_VAPROS1-1_replicaD1
- GSM9568728 Patient_VAPROS1-1_replicaD2
- GSM9568729 Patient_PCa3_Tumor_Replica1
- GSM9568730 Patient_PCa3_Tumor_Replica2
- GSM9568731 Patient_PCa3_Tumor_Replica3
- GSM9568732 Patient_PCa3_Tumor_Replica4
- GSM9568733 Patient_PCa6_Normal_ReplicaA
- GSM9568734 Patient_PCa6_Normal_ReplicaB
- GSM9568735 Patient_PCa6_Normal_ReplicaC
- GSM9568736 Patient_PCa6_Tumor_Replica1
- GSM9568737 Patient_PCa6_Tumor_Replica2
- GSM9568738 Patient_PCa6_Tumor_Replica3
- GSM9568739 Patient_PCa6_Tumor_Replica4
- GSM9568740 Liver_mCRPC
- GSM9568741 Sphenoid_mCRPC
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