Characterization of the gene signature correlated with favorable response to chemoradiotherapy in rectal cancer: A hypothesis-generating study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36621808", "kind": "science-record", "revision": 4, "content_hash": "sha256:3a73ec66926d59a9bab509dc24a3185b28dd17b1f2585bc45fca178f7ac28b57", "created_at": "2026-11-01T19:01:10Z", "updated_at": "2026-11-01T22:51:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Characterization of the gene signature correlated with favorable response to chemoradiotherapy in rectal cancer: A hypothesis-generating study.", "doi": "10.1002/cam4.5586", "pmid": "36621808", "authors": ["Seung Hyuck Jeon", "Eui Kyu Chie"], "journal": "Cancer medicine", "year": 2023, "abstract": "PURPOSE: This study aimed to define the gene signature associated with response to neoadjuvant chemoradiotherapy (nCRT), or chemoradiosensitivity (CRS) signature, in rectal cancer, and investigate the correlation between the CRS signature and characteristics of tumor.\nMATERIALS AND METHODS: Three public microarray datasets of pre-nCRT rectal cancer were used to discover and validate the CRS signature, and the pathway analysis of the CRS signature was performed. Patients in The Cancer Genome Atlas (TCGA) dataset were stratified according to the CRS signature enrichment score, and mutational profile and proportions of infiltrated immune cells were compared.\nRESULTS: In the discovery dataset (GSE53781), 95 genes were upregulated in complete responders compared to non-complete responders and defined as the CRS signature. Pathways regarding DNA replication and repair processes as well as inflammatory response were enriched in the CRS signature. In the validation datasets (GSE35452 and GSE45404), patients with favorable response to nCRT exhibited higher enrichment score of the CRS. In TCGA-READ cohort, patients with high CRS signature harbored KRAS mutation in lower frequency than those with low CRS signature. In addition, proportions of proinflammatory immune cells were higher, but proportion of immunosuppressive M2 macrophages was lower in patients with high CRS signature than those with low CRS signature.\nCONCLUSIONS: The current integrative bioinformatic analysis suggests the CRS signature and showed that the CRS signature is associated with dissimilar mutational profile and increased immune response. The discovered CRS signature and related characteristics may serve as candidate of stratification factor in upcoming studies for rectal cancer.", "claims": [{"id": "claim-method", "statement": "Based on the normalized expression, the empirical Bayes method was used to perform differential expression analysis in an R package limma.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36621808", "locator": "sections[4] \"Definition and characterization of gene signature\" paragraph 2", "quote": "Based on the normalized expression, the empirical Bayes method was used to perform differential expression analysis in an R package limma."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are openly accessible through the Gene Expression Omnibus (GEO) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36621808", "locator": "sections[17] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data that support the findings of this study are openly accessible through the Gene Expression Omnibus (GEO) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In TCGA-READ, the high-CRS group had less frequent KRAS mutation, greater activated NK-cell and dendritic-cell infiltration, and less M2 macrophage infiltration than the low-CRS group.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36621808", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In TCGA‐READ cohort, patients with high CRS signature harbored KRAS mutation in lower frequency than those with low CRS signature."}, {"asset": "source:pmid:36621808", "locator": "sections[10] \"Association between the CRS signature and mutation profiles of cancer\" paragraph 5", "quote": "Among the analyzed genes, KRAS mutation was less frequent in patients with high CRS signature (23.8% vs. 48.8%, p = 0.030) than those with low CRS signature."}, {"asset": "source:pmid:36621808", "locator": "sections[11] \"Association between the CRS signature and immune cell infiltration into cancer\" paragraph 2", "quote": "Activated NK cells were significantly more frequent in tumor with high CRS signature compared to low CRS signature (2.80% vs. 1.48%, p = 0.038; Figure 3A)."}, {"asset": "source:pmid:36621808", "locator": "sections[11] \"Association between the CRS signature and immune cell infiltration into cancer\" paragraph 2", "quote": "Activated dendritic cells were also significantly more abundant in tumor with high CRS signature than low CRS signature (1.20% vs. 0.40%, p = 0.011; Figure 3C)."}, {"asset": "source:pmid:36621808", "locator": "sections[11] \"Association between the CRS signature and immune cell infiltration into cancer\" paragraph 2", "quote": "On contrary, the proportion of immunosuppressive M2 macrophages was significantly lower in tumor with high CRS signature than low CRS signature (17.91% vs. 22.38%, p = 0.026; Figure 3D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "In TCGA-READ, the high-CRS group had less frequent KRAS mutation, greater activated NK-cell and dendritic-cell infiltration, and less M2 macrophage infiltration than the low-CRS group.", "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:36621808"], "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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