Identification of a 5-Hydroxymethylation Signature in Circulating Cell-Free DNA for the Noninvasive Detection of Colorectal Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36276281", "kind": "science-record", "revision": 5, "content_hash": "sha256:723fb00f4ba3b7f620c6decb9cf1d29d5476e42669a5dc64ab8b0a23c0726395", "created_at": "2026-11-01T18:15:41Z", "updated_at": "2026-11-01T22:50:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a 5-Hydroxymethylation Signature in Circulating Cell-Free DNA for the Noninvasive Detection of Colorectal Cancer.", "doi": "10.1155/2022/3798741", "pmid": "36276281", "authors": ["Hongwei Liu", "Tao Tang", "Huixian Zhang", "Weiren Ting", "Peng Zhou", "Ying Luo", "Huaxing Qi", "Yanmei Liu", "Yongxin Liu", "Meifang Zhou", "Weiguo Yin", "Jinduan Lin"], "journal": "Journal of oncology", "year": 2022, "abstract": "Background: As a crucial epigenetic modification, DNA 5-hydroxymethylcytosine (5-hmC) plays a key role during colorectal cancer (CRC) carcinogenesis. Nevertheless, the levels of 5-hmC-related genes in the circulating DNA of CRC remain largely unknown.\nMethods and Results: The GSE81314 dataset from the Gene Expression Omnibus (GEO), which was generated by chemical marking-based low-input shotgun sequencing to detect 5-hmC in circulating cell-free DNA (cfDNA) was used in the present study. The GSE81314 dataset includes data for 8 plasma samples from healthy individuals and 4 plasma samples from CRC patients. The difference in the 5-hmC levels in cfDNA between the CRC group and healthy individuals was analyzed by the differentially expressed genes (DEG) package. Weighted gene coexpression network analysis (WGCNA) was conducted to analyze gene coexpression modules associated with sample characteristics. DEG analysis identified 19 upregulated and 9 downregulated 5-hmC-related genes. WGCNA showed that the pink, purple, and brown modules, which contain 531 genes in total, were significantly correlated with CRC (0.66, 0.61, and -0.59, respectively). We used gene set enrichment analysis (GSEA) software to compare 5-hmC-related genes and pathways between CRC patients and healthy controls. We further performed a protein-protein interaction (PPI) analysis and identified 4 nodes (LCN2, LRG1, S100P, and TACSTD2) that played key roles in the network, and we analyzed the expression of these nodes S100P in the GEPIA database. Consistent with the 5-hmC levels in CRC patient plasma, our external validation results from the GEPIA and UALCAN databases showed that LCN2, LRG1, S100P, and TACSTD2 were highly expressed in CRC tissue compared with controls. The DNA promoter methylation levels of LCN2, LRG1, and S100P were lower in CRC tissue than in normal control tissue.\nConclusion: The present findings suggest that abnormality in cell-free DNA hydroxylation in plasma may be associated with CRC. In addition, the 5-hmC levels of LCN2, LRG1, S100P, and TACSTD2 in circulating cfDNA may be used as potential noninvasive markers for CRC.", "claims": [{"id": "claim-method", "statement": "We analyzed the DEG to evaluate the different 5-hmC levels of cfDNA in plasma between healthy individuals and CRC patients by the limma package [14].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36276281", "locator": "sections[4] \"2.2. DEG Analysis\" paragraph 2", "quote": "We analyzed the DEG to evaluate the different 5-hmC levels of cfDNA in plasma between healthy individuals and CRC patients by the limma package [14]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36276281", "locator": "sections[23] \"Data Availability\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "DEG analysis identified 19 upregulated and 9 downregulated 5-hmC-related genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36276281", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "DEG analysis identified 19 upregulated and 9 downregulated 5-hmC-related genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "DEG analysis identified 19 upregulated and 9 downregulated 5-hmC-related genes.", "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:36276281"], "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:GSE81314"], "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:GSE81314"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36276281", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/3798741", "sha256": 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