ArticleProstate cancer and prostatic diseases2022
Transcriptome subtyping of metastatic Castration Resistance Prostate Cancer (mCRPC) for the precision therapeutics: an in silico analysis.
Article in Prostate cancer and prostatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Transcriptomic Approaches to Cardiomyocyte-Biomaterial Interactions: A Review.ACS biomaterials science & engineering · 2024Review
- Preparation, Optimization, and In-Vitro Evaluation of Brusatol- and Docetaxel-Loaded Nanoparticles for the Treatment of Prostate Cancer.Pharmaceutics · 2024Article
- Identification and validation of cuproptosis related genes and signature markers in bronchopulmonary dysplasia disease using bioinformatics analysis and machine learning.BMC medical informatics and decision making · 2023Article
- mCancers · 2022Article
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5 authors.
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Abstract
backgroundMen with metastatic prostate cancer who are treated with androgen deprivation therapy (ADT) typically develop therapeutic resistance eventually and have a dismal outcome. Moreover, the limited survival benefit observed in only a proportion of patients receiving novel therapeutics including immune checkpoint blockade and PARP inhibitors suggests the biological heterogeneity of mCRPCs.
methodsTo understand the heterogeneity of mCRPC, we analyzed the transcriptome of 231 mCRPCs and identified four disparate biological subtypes (Basal, Homologous Recombination Repair (HRR), Neuroendocrine and Luminal). The package "randomForest" was used to construct a Random Forest model. Circular plots were used for visualization of TMPRSS2-ERG fusion in each subtype.
resultsThe Luminal subtype of mCRPCs has higher Androgen Receptor (AR) expression and copy number alterations as compared with the other subtypes. Genes in HRR pathway are relatively downregulated in most subtypes regardless of the genetic alterations, except for the HRR and NE subtypes, suggesting potential resistance of the HRR and NE mCRPCs to PARP inhibitor treatment. The HRR subtype has relatively more immune cell infiltration and higher expression of immune checkpoints, highlighting that the efficacy of immunotherapy should be evaluated in this particular subtype. TMPRSS2-ERG fusion is the most frequent gene fusion in all mCRPCs, and the Basal subtype has a higher frequency of this fusion than the other subtypes.
conclusionsOur results reveal that the stratification of mCRPC according to transcriptome is informative of personalized therapeutics in the treatment of mCRPCs. The predictive capacity of the transcriptome subtyping of mCRPC warrants further exploration in the future.
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