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pmid:38260290
Higher Inflammatory Response in Hepatocellular Carcinoma is Associated with Immune Cell Infiltration and a Better Outcome.
Masanori Oshi · Kohei Chida · Arya Mariam Roy · Gabriella Kim Mann · Nan An · Li Yan · Itaru Endo · Kazuaki Takabe
Research square · 2024 doi:10.21203/rs.3.rs-3768964/v1
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Experiment
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Analysis
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Execution
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Complete file
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Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC.\nMethods: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the \"INFLAMMATORY_RESPONSE\" gene set.\nResults: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p<0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p<0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p<0.01) and cytolytic activity (p<0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).\nConclusion: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and better patient prognosis.", "claims": [{"id": "claim-method", "statement": "Survival analysis was performed used log-rank test and Cox proportional hazards.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38260290", "locator": "sections[7] \"Statistical analysis\" paragraph 2", "quote": "Survival analysis was performed used log-rank test and Cox proportional hazards."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the cohorts/datasets used in this study; The Cancer Genome Atlas (TCGA) and GO cohorts are all publicly available without any restrictions via cBioportal or Gene Expression Omnibus (GEO).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38260290", "locator": "sections[21] \"Data Availability:\" paragraph 2", "quote": "All the cohorts/datasets used in this study; The Cancer Genome Atlas (TCGA) and GO cohorts are all publicly available without any restrictions via cBioportal or Gene Expression Omnibus (GEO)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38260290", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008).", "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:38260290"], "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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