Development of a novel, clinically relevant anoikis-related gene signature to forecast prognosis in patients with prostate cancer.

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Methods: Based on anoikis-related genes and The Cancer Genome Atlas (TCGA) data, anoikis-related molecular subtypes were identified, and their differences in disease-free survival (DFS), stemness, clinical features, and immune infiltration patterns were compared. Differential expression analysis of the two subtypes and weighted gene co-expression network analysis (WGCNA) were employed to identify clinically relevant anoikis-related differentially expressed genes (DEGs) between subtypes, which were then selected to construct a prognostic signature. The clinical utility of the signature was verified using the validation datasets GSE116918 and GSE46602. A nomogram was established to predict patient survival. Finally, differentially enriched hallmark gene sets were revealed between the different risk groups. Results: Two anoikis-related molecular subtypes were identified, and cluster 1 had poor prognosis, higher stemness, advanced clinical features, and differential immune cell infiltration. Next, 13 clinically relevant anoikis-related DEGs were identified, and five of them (CKS2, CDC20, FMOD, CD38, and MSMB) were selected to build a prognostic signature. This gene signature had a high prognostic value. A nomogram that combined Gleason score, T stage, and risk score could accurately predict patient survival. Furthermore, gene sets closely related with DNA repair were differentially expressed in the different risk groups. Conclusion: A novel, clinically relevant five-anoikis-related gene signature was a powerful prognostic biomarker for PC.", "claims": [{"id": "claim-method", "statement": "The genes with p-value < 0.05 were considered prognosis-related and were selected for further LASSO Cox regression analysis (Tibshirani, 1997) using the glmnet package (version 2.0-18) (Friedman et al., 2009). The optimal combination of prognosis-related genes was selected using 20-fold cross-validation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37719710", "locator": "sections[11] \"2.9 Construction and validation of the prognostic signature\" paragraph 2", "quote": "The genes with p-value < 0.05 were considered prognosis-related and were selected for further LASSO Cox regression analysis (Tibshirani, 1997) using the glmnet package (version 2.0-18) (Friedman et al., 2009). The optimal combination of prognosis-related genes was selected using 20-fold cross-validation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37719710", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A five-anoikis-related gene signature comprising CKS2, CDC20, FMOD, CD38, and MSMB was established as a prognostic biomarker for prostate cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37719710", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "A novel, clinically relevant five-anoikis-related gene signature was a powerful prognostic biomarker for PC."}, {"asset": "source:pmid:37719710", "locator": "sections[20] \"3.5 The prognostic signature was constructed based on five clinically relevant anoikis-related genes\" paragraph 2", "quote": "The optimal gene combination was screened using LASSO Cox regression analysis (Figure 5C), ultimately leading to a prognostic signature constructed using five genes: cyclin-dependent kinases regulatory subunit 2 (CKS2), cell division cycle 20 (CDC20), fibromodulin (FMOD), CD38 molecule (CD38), and microseminoprotein beta (MSMB)."}, {"asset": "source:pmid:37719710", "locator": "sections[20] \"3.5 The prognostic signature was constructed based on five clinically relevant anoikis-related genes\" paragraph 2", "quote": "Furthermore, the areas under the ROC curve (AUC) of the prognostic signature for evaluating the 1-, 3-, and 5-year survival probabilities of the TCGA-PRAD samples were 0.782, 0.72, and 0.67, respectively, and those in the GSE62452 samples were 0.606, 0.692, and 0.689, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A five-anoikis-related gene signature comprising CKS2, CDC20, FMOD, CD38, and MSMB was established as a prognostic biomarker for prostate cancer.", "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:37719710"], "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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