Unveiling mitophagy-mediated molecular heterogeneity and development of a risk signature model for colorectal cancer by integrated scRNA-seq and bulk RNA-seq analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37886241", "kind": "science-record", "revision": 2, "content_hash": "sha256:4ce113c0866644adccf5cbf961260da48f5eb2622d9ff117d7fb76f605abde1f", "created_at": "2026-11-01T19:02:45Z", "updated_at": "2026-11-01T21:31:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unveiling mitophagy-mediated molecular heterogeneity and development of a risk signature model for colorectal cancer by integrated scRNA-seq and bulk RNA-seq analysis.", "doi": "10.1093/gastro/goad066", "pmid": "37886241", "authors": ["Han Gao", "Qi Zou", "Linyun Ma", "Keyu Cai", "Yi Sun", "Li Lu", "Donglin Ren", "Bang Hu"], "journal": "Gastroenterology report", "year": 2023, "abstract": "Background: Accumulating researchers have recognized mitophagy as a key player in tumors, but few studies have investigated its role in the tumor microenvironment (TME). Advances in the technology of single-cell RNA sequencing (scRNA-seq) have allowed unveiling the concealed features of the TME at cellular resolution. This study aimed to elucidate the role of mitophagy within the TME of colorectal cancer (CRC) and to establish a mitophagy-mediated risk model.\nMethods: We assessed mitophagy-related pathway activities at both single-cell and tissue levels. Subsequently, an unsupervised clustering algorithm was employed to identify mitophagy-mediated subtypes. Furthermore, we developed a mitophagy-mediated risk signature (MMRS) using least absolute shrinkage and selection operator (LASSO) Cox analysis and constructed a MMRS model incorporating the risk score and clinical variables. Subsequently, we used quantitative reverse transcription polymerase chain reaction analysis to verify the expression of the screened genes.\nResults: We retrieved and annotated a total of 14,719 cells from eight samples in the scRNA-seq GSE132465 data set. The activities of mitophagy-related pathways were uniformly upregulated in cancer cells. Integrating with bulk RNA-seq data, we identified two mitophagy-mediated clusters (C1 and C2) with distinct characteristics and prognoses. C2 was identified as a mitophagy-high cluster. Then, we developed a five-gene MMRS via LASSO Cox analysis in The Cancer Genome Atlas (TCGA) cohort. We utilized the GSE39582 cohort to validate the efficacy of our model. The expression of CX3CL1 and INHBB was upregulated in CRC tissues.\nConclusions: The present study identified two mitophagy-mediated CRC subtypes with distinct features. Our MMRS may provide potential therapeutic strategies for CRC. The findings of our work offer novel insights into the involvement of mitophagy in CRC.", "claims": [{"id": "claim-method", "statement": "The pathway activity was analysed using the escape package (version 1.10.0) and gene set variation analysis (GSVA) package (version 1.46.0) for scRNA-seq and bulk RNA-seq data, respectively [15].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37886241", "locator": "sections[5] \"Activity evaluation of mitophagy-related pathways\" paragraph 2", "quote": "The pathway activity was analysed using the escape package (version 1.10.0) and gene set variation analysis (GSVA) package (version 1.46.0) for scRNA-seq and bulk RNA-seq data, respectively [15]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Supplementary data is available at Gastroenterology Report online.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37886241", "locator": "sections[30] \"Supplementary Data\" paragraph 2", "quote": "Supplementary data is available at Gastroenterology Report online."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The activities of mitophagy-related pathways were uniformly upregulated in cancer cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37886241", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The activities of mitophagy-related pathways were uniformly upregulated in cancer cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The activities of mitophagy-related pathways were uniformly upregulated in cancer cells.", "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:37886241"], "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:GSE132465"], "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:GSE132465"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37886241", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/gastro/goad066", "sha256": 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