Apoptosis related genes mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide immunotherapy in bladder cancer.

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The purpose of this study is to identify the diagnostic signature factors related to bladder cancer (BLCA) through apoptosis related genes (ARGs). Clinicopathological parameters and transcriptomics data of 1,440 BLCA patients were obtained from 7 datasets (GSE13507, GSE31684, GSE32548, GSE32894, GSE48075, TCGA-BLCA, and IMvigor210). We first identified prognosis-related ARGs in BLCA and used them to construct two ARGs molecular subtypes by using consensus clustering algorithm. By using principal component analysis algorithms, a ARGscore was constructed to quantify the index of individualized patient. High ARGscore correlated with progressive malignancy and poor outcomes in BLCA patients. High ARGscore was associated with higher immune cell, higher estimate scores, higher stromal scores, higher immune scores, higher immune checkpoint, and lower tumor purity, which was consistent with the \"immunity tidal model theory\". Preclinically, BLCA immunotherapy cohorts confirmed patients with low ARGscore demonstrated significant therapeutic advantages and clinical benefits. These findings contribute to our understanding of ARGs and immunotherapy in BLCA. The ARGscore is a potentially useful tool to predict the prognosis and immunotherapy in BLCA.", "claims": [{"id": "claim-method", "statement": "The association between ARGs regulators expression and prognosis was evaluated using univariate Cox regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37118734", "locator": "sections[13] \"Statistical methods\" paragraph 2", "quote": "The association between ARGs regulators expression and prognosis was evaluated using univariate Cox regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data used in the study can be downloaded from the TCGA data repository (https://portal.gdc.cancer.gov/) and the GEO database (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37118734", "locator": "sections[29] \"notes\" paragraph 1", "quote": "All data used in the study can be downloaded from the TCGA data repository (https://portal.gdc.cancer.gov/) and the GEO database (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The high ARGscore group had worse overall survival than the low ARGscore group across multiple independent datasets.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "In both patient sets, patients in the high ARGscore group had a worse OS than in the low ARGscore group (GSE13507: HR = 2.35, 95% CI = 1.45–3.81, P = 0.001, GSE31684: HR = 2.02, 95% CI = 1.04–3.93, P = 0.038, GSE32548: HR = 2.30, 95% CI = 1.00–5.25, P = 0.049, GSE32894: HR = 2.17, 95% CI = 1.05–4.47, P = 0.037, GSE48075: HR = 1.93, 95% CI = 1.02–3.66, P = 0.044, TCGA-BLCA: HR = 1.37, 95% CI = 1.01–1.85, P = 0.043)"}, "evidence": [{"asset": "source:pmid:37118734", "locator": "sections[18] \"ARGscore is a robust prognosis factor in BLCA\" paragraph 2", "quote": "In both patient sets, patients in the high ARGscore group had a worse OS than in the low ARGscore group (GSE13507: HR = 2.35, 95% CI = 1.45–3.81, P = 0.001, GSE31684: HR = 2.02, 95% CI = 1.04–3.93, P = 0.038, GSE32548: HR = 2.30, 95% CI = 1.00–5.25, P = 0.049, GSE32894: HR = 2.17, 95% CI = 1.05–4.47, P = 0.037, GSE48075: HR = 1.93, 95% CI = 1.02–3.66, P = 0.044, TCGA-BLCA: HR = 1.37, 95% CI = 1.01–1.85, P = 0.043)"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The high ARGscore group had worse overall survival than the low ARGscore group across multiple independent datasets.", "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:37118734"], "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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