ArticleProstate cancer and prostatic diseases2021
Prostate epithelial genes define therapy-relevant prostate cancer molecular subtype.
Article in Prostate cancer and prostatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Efficacy and safety of triple or dual therapies for metastatic hormone-sensitive prostate cancer: a systematic review and Bayesian network meta-analysis.Future oncology (London, England) · 2026Pooled it
- ERG Orchestrates a Dedifferentiation-Senescence-Inflammation Triad in Prostate Cancer.Molecular cancer research : MCR · 2026Article
- Clinical significance of primary tumor progression in metastatic hormone-sensitive prostate cancer.Prostate international · 2025Article
- Comparative Transcriptomes of Canine and Human Prostate Cancers Identify Mediators of Castration Resistance.Veterinary and comparative oncology · 2024Article
- Application and new findings of scRNA-seq and ST-seq in prostate cancer.Cell regeneration (London, England) · 2024Review
- Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review.Cancers · 2024Review
- Case report: Exceptional and durable response to Radium-223 and suspension of androgen deprivation therapy in a metastatic castration-resistant prostate cancer patient.Frontiers in oncology · 2024Article
- Metabolomic profiles of intact tissues reflect clinically relevant prostate cancer subtypes.Journal of translational medicine · 2023Article
- Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140,000 subjects.Human molecular genetics · 2023Article
- Review
- Circulating Tumor DNA Analysis on Metastatic Prostate Cancer with Disease Progression.Cancers · 2023Article
- Single-cell omics traces the heterogeneity of prostate cancer cells and the tumor microenvironment.Cellular & molecular biology letters · 2023Review
- Molecular classifications of prostate cancer: basis for individualized risk stratification and precision therapy.Annals of medicine · 2023Review
- Characteristics of BRCA2 Mutated Prostate Cancer at Presentation.International journal of molecular sciences · 2022Article
- Understanding and targeting prostate cancer cell heterogeneity and plasticity.Seminars in cancer biology · 2022Review
- Characterization of Immune-Based Molecular Subtypes and Prognostic Model in Prostate Adenocarcinoma.Genes · 2022Article
- Review
- Article
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11 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
objectivesTranscriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation. MATERIALS AND
methodsTo focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting.
resultsWe identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy.
conclusionWe propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents.
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