Identification of a Radiosensitivity Molecular Signature Induced by Enzalutamide in Hormone-sensitive and Hormone-resistant Prostate Cancer Cells.

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A novel androgen receptor (AR) antagonist, enzalutamide (ENZA) has recently been demonstrated to enhance the effect of radiation (XRT) by impairing the DNA damage repair process. This study aimed to identify a radiosensitive gene signature induced by ENZA in the PCa cells and to elucidate the biological pathways which influence this radiosensitivity. We treated LNCaP (AR-positive, hormone-sensitive PCa cells) and C4-2 (AR-positive, hormone-resistant PCa cells) cells with ENZA alone and in combination with androgen deprivation therapy (ADT) and XRT. Using one-way ANOVA on the gene expression profiling, we observed significantly differentially expressed (DE) genes in inflammation-and metabolism-related genes in hormone-sensitive and hormone-resistant PCa cell lines respectively. Survival analysis in both the TCGA PRAD and GSE25136 datasets suggested an association between the expression of these genes and time to recurrence. These results indicated that ENZA alone or in combination with ADT enhanced the effect of XRT through immune and inflammation-related pathways in LNCaP cells and metabolic-related pathways in C4-2 cells. Kaplan-Meier analysis and Cox proportional hazard models showed that low expression of all the candidate genes except for PTPRN2 were associated with tumor progression and recurrence in a PCa cohort.", "claims": [{"id": "claim-method", "statement": "We performed a univariate Cox proportional hazards survival model and found that the expression of a set of 10 genes was associated with time to recurrence (p < 0.05 without any correction for multiple testing).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31221986", "locator": "sections[8] \"Analysis of the associations between candidate genes and risk of recurrence\" paragraph 2", "quote": "We performed a univariate Cox proportional hazards survival model and found that the expression of a set of 10 genes was associated with time to recurrence (p < 0.05 without any correction for multiple testing)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data have been submitted to the public functional genomics data repository Gene Expression Omnibus (GEO) under the accession number GSE126881.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31221986", "locator": "sections[16] \"Expression microarray analysis\" paragraph 3", "quote": "The microarray data have been submitted to the public functional genomics data repository Gene Expression Omnibus (GEO) under the accession number GSE126881."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31221986"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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