A novel strategy for precise prognosis management and treatment option in colon adenocarcinoma with TP53 mutations.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36843983", "kind": "science-record", "revision": 2, "content_hash": "sha256:50c181959220e012328f7a552daf51e625c34e8765bb309f44025e7d3b78e5e2", "created_at": "2026-11-01T19:01:27Z", "updated_at": "2026-11-01T21:30:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel strategy for precise prognosis management and treatment option in colon adenocarcinoma with TP53 mutations.", "doi": "10.3389/fsurg.2023.1079129", "pmid": "36843983", "authors": ["Lei Niu", "Langbiao Liu", "Jun Cai"], "journal": "Frontiers in surgery", "year": 2023, "abstract": "Background: TP53 is one of the most frequent mutated genes in colon cancer. Although colon cancer with TP53 mutations has a high risk of metastasis and worse prognosis generally, it showed high heterogeneity clinically.\nMethods: A total of 1,412 colon adenocarcinoma (COAD) samples were obtained from two RNA-seq cohorts and three microarray cohorts, including the TCGA-COAD (N = 408), the CPTAC-COAD (N = 106), GSE39582 (N = 541), GSE17536 (N = 171) and GSE41258 (N = 186). The LASSO-Cox method was used to establish the prognostic signature based on the expression data. The patients were divided into high-risk and low-risk groups based on the median risk score. The efficiency of the prognostic signature was validated in various cohorts, including TP53-mutant and TP53 wild-type. The exploration of potential therapeutic targets and agents was performed by using the expression data of TP53-mutant COAD cell lines obtained from the CCLE database and the corresponding drug sensitivity data obtained from the GDSC database.\nResults: A 16-gene prognostic signature was established in TP53-mutant COAD. The high-risk group had significantly inferior survival time compared to the low-risk group in all TP53-mutant datasets, while the prognostic signature failed to classify the prognosis of COAD with TP53 wild-type properly. Besides, the risk score was the independent poor factor for the prognosis in TP53-mutant COAD and the nomogram based on the risk score was also shown good predictive efficiency in TP53-mutant COAD. Moreover, we identified SGPP1, RHOQ, and PDGFRB as potential targets for TP53-mutant COAD, and illuminated that the high-risk patients might benefit from IGFR-3801, Staurosporine, and Sabutoclax.\nConclusion: A novel prognostic signature with great efficiency was established especially for COAD patients with TP53 mutations. Besides, we identified novel therapeutic targets and potential sensitive agents for TP53-mutant COAD with high risk. Our findings provided not only a new strategy for prognosis management but also new clues for drug application and precision treatment in COAD with TP53 mutations.", "claims": [{"id": "claim-method", "statement": "LASSO-Cox regression method (19, 20) was performed by the “glmnet” R package in the training set and the risk score of each sample were calculated based on the coefficient and expression level of each selected genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36843983", "locator": "sections[5] \"Least absolute shrinkage and selection operator (LASSO) analysis\" paragraph 2", "quote": "LASSO-Cox regression method (19, 20) was performed by the “glmnet” R package in the training set and the risk score of each sample were calculated based on the coefficient and expression level of each selected genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA-COAD dataset: https://portal.gdc.cancer.gov; CPTAC-COAD dataset: https://www.cbioportal.org/study/summary?id=coad_cptac_2019; GSE39582, GSE17536, GSE41258: https://www.ncbi.nlm.nih.gov/geo/; CCLE database: https://portals.broadinstitute.org/ccle/; GDSC database: https://www.cancerrxgene.org/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36843983", "locator": "sections[18] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA-COAD dataset: https://portal.gdc.cancer.gov; CPTAC-COAD dataset: https://www.cbioportal.org/study/summary?id=coad_cptac_2019; GSE39582, GSE17536, GSE41258: https://www.ncbi.nlm.nih.gov/geo/; CCLE database: https://portals.broadinstitute.org/ccle/; GDSC database: https://www.cancerrxgene.org/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The LASSO-Cox method was used to establish a 16-gene prognostic signature for prognosis prediction in TP53-mutant COAD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36843983", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A 16-gene prognostic signature was established in TP53-mutant COAD."}, {"asset": "source:pmid:36843983", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The LASSO-Cox method was used to establish the prognostic signature based on the expression data."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The LASSO-Cox method was used to establish a 16-gene prognostic signature for prognosis prediction in TP53-mutant COAD.", "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:36843983"], "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:GSE17536"], "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:GSE17536"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36843983", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fsurg.2023.1079129", "sha256": "sha256:8364b0b5fc62ed8ea04be834dd018e6f7be94a20d3f16e48664af55389b11e5f", "bytes": 38081, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fsurg.2023.1079129", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9947352", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17536", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17536", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17536", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA-COAD dataset: https://portal.gdc.cancer.gov; CPTAC-COAD dataset: https://www.cbioportal.org/study/summary?id=coad_cptac_2019; GSE39582, GSE17536, GSE41258: https://www.ncbi.nlm.nih.gov/geo/; CCLE database: https://portals.broadinstitute.org/ccle/; GDSC database: https://www.cancerrxgene.org/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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