Molecular subtype identification and prognosis stratification by a metabolism-related gene expression signature in colorectal cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34193202", "kind": "science-record", "revision": 6, "content_hash": "sha256:2bf139d77c4d5b64455138f2c69a00a6e0cec713f2291781faaa4ac4bb49fcd6", "created_at": "2026-11-01T15:41:41Z", "updated_at": "2026-11-01T21:25:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Molecular subtype identification and prognosis stratification by a metabolism-related gene expression signature in colorectal cancer.", "doi": "10.1186/s12967-021-02952-w", "pmid": "34193202", "authors": ["Dagui Lin", "Wenhua Fan", "Rongxin Zhang", "Enen Zhao", "Pansong Li", "Wenhao Zhou", "Jianhong Peng", "Liren Li"], "journal": "Journal of translational medicine", "year": 2021, "abstract": "BACKGROUND: Metabolic reprograming have been associated with cancer occurrence and progression within the tumor immune microenvironment. However, the prognostic potential of metabolism-related genes in colorectal cancer (CRC) has not been comprehensively studied. Here, we investigated metabolic transcript-related CRC subtypes and relevant immune landscapes, and developed a metabolic risk score (MRS) for survival prediction.\nMETHODS: Metabolism-related genes were collected from the Molecular Signatures Database and metabolic subtypes were identified using an unsupervised clustering algorithm based on the expression profiles of survival-related metabolic genes in GSE39582. The ssGSEA and ESTIMATE methods were applied to estimate the immune infiltration among subtypes. The MRS model was developed using LASSO Cox regression in the GSE39582 dataset and independently validated in the TCGA CRC and GSE17537 datasets.\nRESULTS: We identified two metabolism-related subtypes (cluster-A and cluster-B) of CRC based on the expression profiles of 539 survival-related metabolic genes with distinct immune profiles and notably different prognoses. The cluster-B subtype had a shorter OS and RFS than the cluster-A subtype. Eighteen metabolism-related genes that were mostly involved in lipid metabolism pathways were used to build the MRS in GSE39582. Patients with higher MRS had worse prognosis than those with lower MRS (HR 3.45, P < 0.001). The prognostic role of MRS was validated in the TCGA CRC (HR 2.12, P = 0.00017) and GSE17537 datasets (HR 2.67, P = 0.039). Time-dependent receiver operating characteristic curve and stratified analyses revealed the robust predictive ability of the MRS in each dataset. Multivariate Cox regression analysis indicted that the MRS could predict OS independent of TNM stage and age.\nCONCLUSIONS: Our study provides novel insight into metabolic heterogeneity and its relationship with immune landscape in CRC. The MRS was identified as a robust prognostic marker and may facilitate individualized therapy for CRC patients.", "claims": [{"id": "claim-method", "statement": "Further, the expression profiles of 539 survival-related metabolic genes were employed to performed k-means unsupervised clustering by the “ConsensusClusterPlus” package with 1000 repetitions [21, 22].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34193202", "locator": "sections[4] \"Identification of metabolism-related subtypes\" paragraph 2", "quote": "Further, the expression profiles of 539 survival-related metabolic genes were employed to performed k-means unsupervised clustering by the “ConsensusClusterPlus” package with 1000 repetitions [21, 22]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed in this study are available in public databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34193202", "locator": "sections[28] \"notes\" paragraph 1", "quote": "The datasets analyzed in this study are available in public databases."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34193202"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE17537"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE17537"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34193202", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-021-02952-w", "sha256": 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"access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed in this study are available in public databases.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM437270", "GSM437271", "GSM437272", "GSM437273", "GSM437274", "GSM437275", "GSM437276", "GSM437277", "GSM437278", "GSM437279", "GSM437280", "GSM437281", "GSM437282", "GSM437283", "GSM437284", "GSM437285", "GSM437286", "GSM437287", "GSM437288", "GSM437289", "GSM437290", "GSM437291", "GSM437292", "GSM437293", "GSM437294", "GSM437295", "GSM437296", "GSM437297", "GSM437298", "GSM437299", "GSM437300", "GSM437301", "GSM437302", "GSM437303", "GSM437304", "GSM437305", "GSM437306", "GSM437307", "GSM437308", "GSM437309", "GSM437310", "GSM437311", "GSM437312", "GSM437313", "GSM437314", "GSM437315", "GSM437316", "GSM437317", "GSM437318", "GSM437319", "GSM437320", "GSM437321", "GSM437322", "GSM437323", "GSM437324"], "sample_count": 55, "group_sizes": null, "group_sizes_basis": 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