A bioinformatics framework to identify the biomarkers and potential drugs for the treatment of colorectal cancer.

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Therefore, it is critical to understand the molecular mechanism of CRC and identify its diagnostic and prognostic biomarkers. The purpose of this study is to reveal the genes involved in the development of CRC and to predict drug candidates that may help treat CRC through bioinformatics analyses. Two independent CRC gene expression datasets including The Cancer Genome Atlas (TCGA) database and GSE104836 were used in this study. Differentially expressed genes (DEGs) were analyzed separately on the two datasets, and intersected for further analyses. 249 drug candidates for CRC were identified according to the intersected DEGs and the Crowd Extracted Expression of Differential Signatures (CREEDS) database. In addition, hub genes were analyzed using Cytoscape according to the DEGs, and survival analysis results showed that one of the hub genes, TIMP1 was related to the prognosis of CRC patients. Thus, we further focused on drugs that could reverse the expression level of TIMP1. Eight potential drugs with documentary evidence and two new drugs that could reverse the expression of TIMP1 were found among the 249 drugs. In conclusion, we successfully identified potential biomarkers for CRC and achieved drug repurposing using bioinformatics methods. Further exploration is needed to understand the molecular mechanisms of these identified genes and drugs/small molecules in the occurrence, development and treatment of CRC.", "claims": [{"id": "claim-method", "statement": "We obtained the OS time of all patients in TCGA database, and estimated the survival probability of CRC patients using Kaplan-Meier method. Kaplan-Meier survival curve was used to estimate the 50th percentile (median) of survival time and compare the survival distribution of two or more groups. Log-rank test was also used to compare the survival differences between groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36238159", "locator": "sections[8] \"Survival analysis\" paragraph 2", "quote": "We obtained the OS time of all patients in TCGA database, and estimated the survival probability of CRC patients using Kaplan-Meier method. Kaplan-Meier survival curve was used to estimate the 50th percentile (median) of survival time and compare the survival distribution of two or more groups. Log-rank test was also used to compare the survival differences between groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TIMP1 was related to the prognosis of CRC patients, and eight potential drugs with documentary evidence and two new drugs that could reverse the expression of TIMP1 were found among the 249 drugs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36238159", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "survival analysis results showed that one of the hub genes, TIMP1 was related to the prognosis of CRC patients."}, {"asset": "source:pmid:36238159", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Eight potential drugs with documentary evidence and two new drugs that could reverse the expression of TIMP1 were found among the 249 drugs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TIMP1 was related to the prognosis of CRC patients, and eight potential drugs with documentary evidence and two new drugs that could reverse the expression of TIMP1 were found among the 249 drugs.", "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:36238159"], "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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