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pmid:36124532
Identification of senescence-related molecular subtypes and key genes for prostate cancer.
De-Chao Feng · Wei-Zhen Zhu · Xu Shi · Qiao Xiong · Jia You · Qiang Wei · Lu Yang
Asian journal of andrology · 2023 doi:10.4103/aja202258
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Experiment
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Complete file
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We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.", "claims": [{"id": "claim-method", "statement": "The log-rank test was used to determine the DEGs related to BCR-free survival in TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36124532", "locator": "sections[2] \"MATERIALS AND METHODS\" paragraph 2", "quote": "The log-rank test was used to determine the DEGs related to BCR-free survival in TCGA database."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The standardized PCa data in The Cancer Genome Atlas (TCGA) database were downloaded from the University of California, Santa Cruz (UCSC) Xena (CA, USA),11 and the matrix of message RNA (mRNA) was extracted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36124532", "locator": "sections[2] \"MATERIALS AND METHODS\" paragraph 2", "quote": "The standardized PCa data in The Cancer Genome Atlas (TCGA) database were downloaded from the University of California, Santa Cruz (UCSC) Xena (CA, USA),11 and the matrix of message RNA (mRNA) was extracted."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients in cluster 2 had a significantly higher risk of biochemical recurrence than patients in cluster 1 in both TCGA and GSE116918.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "In TCGA database, cluster 2 had a significantly higher risk of BCR than cluster 1 (hazard ratio [HR]: 2.20, 95% confidence interval [CI]: 1.31–3.69, P = 0.003; Figure 1d)."}, "evidence": [{"asset": "source:pmid:36124532", "locator": "sections[3] \"RESULTS\" paragraph 2", "quote": "In TCGA database, cluster 2 had a significantly higher risk of BCR than cluster 1 (hazard ratio [HR]: 2.20, 95% confidence interval [CI]: 1.31–3.69, P = 0.003; Figure 1d)."}, {"asset": "source:pmid:36124532", "locator": "sections[3] \"RESULTS\" paragraph 2", "quote": "Cluster 2 was more likely to encounter BCR (HR: 3.67, 95% CI: 2.14–6.29, P < 0.001; Figure 1e) and metastasis (HR: 5.93, 95% CI: 2.50–14.08, P = 0.006; Figure 1f) than cluster 1 in GSE116918."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients in cluster 2 had a significantly higher risk of biochemical recurrence than patients in cluster 1 in both TCGA and GSE116918.", "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:36124532"], "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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