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pmid:36064367
Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy.
Ebrahim Salehitabar · Mohammad Mahdevar · Ali Valipour Motlagh · Farzad Seyed Forootan · Sara Feizbakhshan · Dina Zohrabi · Maryam Peymani
Cancer cell international · 2022 doi:10.1186/s12935-022-02694-9
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Complete file
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We aimed to identify the genes with high heterogeneity of expression (HHE) and their relation with prognosis and drug resistance.\nMETHODS: Two cohort studies, the cancer genome atlas (TCGA) and the GSE39582, were used to discover oncogenes genes with HHE. The relationship between identified genes with clinical and genomic characteristics was evaluated based on TCGA data. Also, the GDSC and CCLE data were used for drug resistance and sensitivity. Sixty CRC samples were used to validate the obtained data by RT-qPCR.\nRESULTS: Findings revealed that 132 genes with HHE were found to be up-regulated in both cohorts and were enriched in pathways such as hypoxia, angiogenesis, and metastasis. Forty-nine of selected genes related to clinical and genomic variables, including stage, common mutations, the tumor site, and microsatellite state that were ignored. The expression level of CXCL1, SFTA2, SELE, and SACS as genes with HHE were predicted survival patients, and RT-qPCR results demonstrated that levels of SELE and SACS had HHE in CRC samples. The expression of many identified genes like BGN, MMP7, COL11A1, FAP, KLK10, and TNFRSE11B was associated with resistance to chemotherapy drugs.\nCONCLUSIONS: Some genes expression, including SELE, SACS, BGN, KLK10, COL11A1, and TNFRSE11B have an oncogenic function with HHE, and their expression can be used as indicators for differing treatment responses and survival rates in CRC.", "claims": [{"id": "claim-method", "statement": "Following that, the expression distributions of 1537 genes identified in both cohort studies were determined using the standard deviation calculation among cancer samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36064367", "locator": "sections[10] \"Identification of 132 genes in CRC as candidate genes with HHE\" paragraph 2", "quote": "Following that, the expression distributions of 1537 genes identified in both cohort studies were determined using the standard deviation calculation among cancer samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Supporting and raw data are available upon a reasonable request to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36064367", "locator": "sections[24] \"Availability of data and materials\" paragraph 2", "quote": "Supporting and raw data are available upon a reasonable request to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The results showed that 132 genes in both studies had highly variable expression (SD > 1) between samples and were selected as candidate genes to continue the analysis (Fig. 1B and Additional file 1: Table S1).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36064367", "locator": "sections[10] \"Identification of 132 genes in CRC as candidate genes with HHE\" paragraph 2", "quote": "The results showed that 132 genes in both studies had highly variable expression (SD > 1) between samples and were selected as candidate genes to continue the analysis (Fig. 1B and Additional file 1: Table S1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The results showed that 132 genes in both studies had highly variable expression (SD > 1) between samples and were selected as candidate genes to continue the analysis (Fig. 1B and Additional file 1: Table S1).", "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:36064367"], "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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RESULTS: Findings revealed that 132 genes w", "th HHE were predicted survival patients, and RT-qPCR results demonstrated that levels of SELE and", "ere used to validate the obtained data by RT-qPCR. 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