A Multi-Center Validated Subtyping Model of Esophageal Cancer Based on Three Metabolism-Related Genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34760709", "kind": "science-record", "revision": 5, "content_hash": "sha256:a94e295c344cf46982ab89b87821a22df6790e83424a5d9de138dbfd372cdeb7", "created_at": "2026-11-01T17:36:27Z", "updated_at": "2026-11-01T22:47:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Multi-Center Validated Subtyping Model of Esophageal Cancer Based on Three Metabolism-Related Genes.", "doi": "10.3389/fonc.2021.772145", "pmid": "34760709", "authors": ["Yu Liu", "Liyu Wang", "Lingling Fang", "Hengchang Liu", "He Tian", "Yujia Zheng", "Tao Fan", "Chunxiang Li", "Jie He"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "Metabolic reprogramming is a hallmark of malignancy. Understanding the characteristics of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) helps uncover novel targets for cancer progression. In this study, 880 metabolism-related genes were identified from microarray data and then filtered to divide patients into two subgroups using consensus clustering, which exhibits significantly different overall survival. After a differential analysis between two subtypes, 3 genes were screened out to construct a two subtypes decision model on the training cohort (GSE53624), defined as high-risk and low-risk subtypes. These risk models were then verified in two public databases (GSE53622 and TCGA-ESCC), an independent cohort of 49 ESCC patients by RT-qPCR and an external cohort of 95 ESCC patients by immunohistochemistry analysis (IHC). Furthermore, the immune cell infiltration of regulatory T cells (Tregs) and plasma cells showed a significant difference between the high and low-risk subtypes in the IHC experiment with 119 ESCC patients. In conclusion, our study indicated that three metabolism-related prognostic genes could stratify patients into subgroups and were associated with immune infiltration, clinical features and clinical outcomes.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate stepwise Cox PHR analyses were used to construct a metabolism-related prognosis mRNA signature based on OS (GSE53624).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34760709", "locator": "sections[5] \"Consensus Clustering and Construction of a Prognostic Signature\" paragraph 3", "quote": "Univariate and multivariate stepwise Cox PHR analyses were used to construct a metabolism-related prognosis mRNA signature based on OS (GSE53624)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: The public datasets GSE53622,GSE53624 and TCGA-ESCC and clinical information for this study can be found in the GEO and TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34760709", "locator": "sections[17] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: The public datasets GSE53622,GSE53624 and TCGA-ESCC and clinical information for this study can be found in the GEO and TCGA database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A three-gene metabolism-related prognostic signature, comprising CD38, INPP5E, and POLR3G, stratified ESCC patients into high- and low-risk groups with significantly different overall survival and was independently validated.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Multivariate Cox analysis also demonstrated that our signature could serve as an independent predictive factor for OS in the GSE53622 (HR =2.172; 95% CI: 1.00-4.68; p=0.048; Figure 3C ) and TCGA (HR =4.251; 95% CI: 1.589-11.37; p=0.004; Figure 3D ) datasets."}, "evidence": [{"asset": "source:pmid:34760709", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In conclusion, our study indicated that three metabolism-related prognostic genes could stratify patients into subgroups and were associated with immune infiltration, clinical features and clinical outcomes."}, {"asset": "source:pmid:34760709", "locator": "sections[13] \"Validation of the Prognostic Value of the Metabolism-Related Prognostic Signature\" paragraph 2", "quote": "Multivariate Cox analysis also demonstrated that our signature could serve as an independent predictive factor for OS in the GSE53622 (HR =2.172; 95% CI: 1.00-4.68; p=0.048; Figure 3C ) and TCGA (HR =4.251; 95% CI: 1.589-11.37; p=0.004; Figure 3D ) datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A three-gene metabolism-related prognostic signature, comprising CD38, INPP5E, and POLR3G, stratified ESCC patients into high- and low-risk groups with significantly different overall survival and was independently validated.", "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:34760709"], "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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