Establishment of cancer-associated fibroblasts-related subtypes and prognostic index for prostate cancer through single-cell and bulk RNA transcriptome.

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In this study, we identified CAF-related molecular subtypes and prognostic index for PCa patients undergoing radical prostatectomy through integrating single-cell and bulk RNA sequencing data. We completed analyses using software R 3.6.3 and its suitable packages. Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI). These genes could clearly divide the PCa patients into two subtypes in TCGA database and the BCR risk of subtype 1 was 13.27 times higher than that of subtype 2 with statistical significance. Similar results were observed in MSKCC2010 and GSE46602 cohorts. In addtion, the molucular subtypes were the independent risk factor of PCa patients. We orchestrated CRGPI based on the above genes and divided 430 PCa patients in TCGA database into high- and low- risk groups according to the median value of this score. We found that high-risk group had significant higher risk of BCR than low-risk group (HR: 5.45). For functional analysis, protein secretion was highly enriched in subtype 2 while snare interactions in vesicular transport was highly enriched in subtype 1. In terms of tumor heterogeneity and stemness, subtype 1 showd higher levels of TMB than subtype 2. In addition, subtype 1 had significant higher activated dendritic cell score than subtype 2. Based on eight CAF-related genes, we developed two prognostic subtypes and constructed a gene prognostic index, which could predict the prognosis of PCa patients very well.", "claims": [{"id": "claim-method", "statement": "In TCGA database, 430 samples with complete BCR information were used, and the p value was smaller than 0.05 using log-rank test for BCR-free survival.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37270661", "locator": "sections[3] \"Data preparation\" paragraph 2", "quote": "In TCGA database, 430 samples with complete BCR information were used, and the p value was smaller than 0.05 using log-rank test for BCR-free survival."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the TCGA (https://www.cancer.gov/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/, accession number: GSE116918 and GSE46602) repositories.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37270661", "locator": "sections[15] \"Data availability\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are available in the TCGA (https://www.cancer.gov/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/, accession number: GSE116918 and GSE46602) repositories."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Single-cell and bulk RNA-sequencing analysis identified eight CAF-related genes used to construct two prognostic molecular subtypes and a CAF-related gene prognostic index for prostate cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37270661", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Single-cell and bulk RNA-sequencing analysis identified eight CAF-related genes used to construct two prognostic molecular subtypes and a CAF-related gene prognostic index 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:37270661"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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