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pmid:38012642
Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics.
Yi Liu · Yanguang Yang · Feng Ni · Guomei Tai · Cenming Yu · Xiaohui Jiang · Ding Wang
Journal of translational medicine · 2023 doi:10.1186/s12967-023-04753-9
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Experiment
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Complete file
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We explored the radiosensitivity related genes of rectal cancer at a multi omics level.\nMETHODS: mRNA expression data and rectum adenocarcinoma (READ) data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus Database (GEO) (GSE150082, GSE60331, GSE46862, GSE46862). Differentially expressed genes between radiotherapy sensitive group and radiotherapy insensitive group were screened. GO analysis and KEGG pathway analysis were performed for differentially expressed genes. Among the differentially expressed genes, five core genes associated with rectal cancer prognosis were selected using random survival forest analysis. For these five core genes, drug sensitivity analysis, immune cell infiltration analysis, TISIDB database immune gene correlation analysis, GSEA enrichment analysis, construction of Nomogram prediction model, transcriptional regulatory network analysis, and qRT-PCR validation was performed on human rectal adenocarcinoma tissue.\nRESULTS: We found that 600 up-regulated genes and 553 down-regulated genes were significantly different between radiotherapy sensitive group and radiotherapy insensitive group in rectal cancer. Five key genes, TOP2A, MATR3, APOL6, JOSD1, and HOXC6, were finally screened by random survival forest analysis. These five key genes were associated with different immune cell infiltration, immune-related genes, and chemosensitivity. A comprehensive transcriptional regulatory network was constructed based on these five core genes. qRT-PCR revealed that MATR3 expression was different in rectal cancer tissues and adjacent non-cancerous tissues, while APOL6, HOXC6, JOSD1, and TOP2A expression was not different.\nCONCLUSION: Five radiosensitivity-related genes related to the prognosis of rectal cancer: TOP2A, MATR3, APOL6, JOSD1, HOXC6, are involved in multiple processes such as immune cell infiltration, immune-related genes, chemosensitivity, signaling pathways and transcriptional regulatory networks and may be potential biomarkers for radiotherapy of rectal cancer.", "claims": [{"id": "claim-method", "statement": "We also ranked the importance of prognostically relevant genes using a random survival forest algorithm (nrep = 1000, which suggests that the number of iterations in Monte Carlo simulations is 1000).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38012642", "locator": "sections[4] \"Random survival forest [10] screening critical genes\" paragraph 2", "quote": "We also ranked the importance of prognostically relevant genes using a random survival forest algorithm (nrep = 1000, which suggests that the number of iterations in Monte Carlo simulations is 1000)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38012642", "locator": "sections[29] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analysed during the current study available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Random survival forest analysis identified five key genes associated with rectal cancer prognosis: TOP2A, MATR3, HOXC6, APOL6, and JOSD1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38012642", "locator": "sections[16] \"Random survival forest analysis of differential genes\" paragraph 2", "quote": "we identified genes with relative importance > 0.3 as final markers, and finally screened five key genes, TOP2A, MATR3, HOXC6, APOL6, and JOSD1 (Fig. 3)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Random survival forest analysis identified five key genes associated with rectal cancer prognosis: TOP2A, MATR3, HOXC6, APOL6, and JOSD1.", "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:38012642"], "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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