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pmid:32209538
Expression of Genes Related to Lipid Handling and the Obesity Paradox in Melanoma: Database Analysis.
Claudia Giampietri · Luana Tomaipitinca · Francesca Scatozza · Antonio Facchiano
JMIR cancer · 2020 doi:10.2196/16974
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Many studies have highlighted the role lipids play in cancer initiation and progression and reported nutritional interventions aimed at improving prognosis and survival. Therefore, there is an increasing interest in the role that fat intake may play in cancer. It is known that there is a relationship between BMI and survival in patients with cancer, and that there is an association between a high-fat diet and increased cancer risk. In some cancers, such as colorectal cancer, obesity and high fat intake are known to increase the risk of cancer initiation and progression. On the contrary, in patients undergoing treatment for melanoma, a higher BMI unexpectedly acts as a protective factor rather than a risk factor; this phenomenon is known as the obesity paradox.\nOBJECTIVE: We aimed to identify the molecular mechanism underlying the obesity paradox, with the expectation that this could indicate new effective strategies to reduce risk factors and improve protective approaches.\nMETHODS: In order to determine the genes potentially involved in this process, we investigated the expression values of lipid-related genes in patients with melanoma or colorectal cancer. We used available data from 2990 patients from 3 public databases (IST [In Silico Transcriptomics] Online, GEO [Gene Expression Omnibus], and Oncomine) in an analysis that involved 3 consecutive validation steps. Of this group, data from 1410 individuals were analyzed in the IST Online database (208 patients with melanoma and 147 healthy controls, as well as 991 patients with colorectal cancer and 64 healthy controls). In addition, 45 melanoma, 18 nevi, and 7 healthy skin biopsies were analyzed in another database, GEO, to validate the IST Online data. Finally, using the Oncomine database, 318 patients with melanoma (312 controls) and 435 patients with colorectal cancer (445 controls) were analyzed.\nRESULTS: In the first and second database investigated (IST Online and GEO, respectively), patients with melanoma consistently showed significantly (P<.001) lower expression levels of 4 genes compared to healthy controls: CD36, MARCO, FABP4, and FABP7. This strong reduction was not observed in patients with colorectal cancer. An additional analysis was carried out on a DNA-TCGA data set from the Oncomine database, further validating CD36 and FABP4.\nCONCLUSIONS: The observed lower expression of genes such as CD36 and FABP4 in melanoma may reduce the cellular internalization of fat and therefore make patients with melanoma less sensitive to a high dietary fat intake, explaining in part the obesity paradox observed in patients with melanoma.", "claims": [{"id": "claim-method", "statement": "Within the scatterplots obtained from the IST Online database analysis, the number of patients falling above or below the chosen threshold were counted and analyzed according to the Fisher exact test using GraphPad Prism 5 (GraphPad Software, Inc).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32209538", "locator": "sections[4] \"Statistical Analysis\" paragraph 2", "quote": "Within the scatterplots obtained from the IST Online database analysis, the number of patients falling above or below the chosen threshold were counted and analyzed according to the Fisher exact test using GraphPad Prism 5 (GraphPad Software, Inc)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We analyzed data from 1410 individuals, including 208 patients with melanoma and 147 healthy controls, and 991 patients with colorectal cancer and 64 healthy controls.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32209538", "locator": "sections[3] \"Overview\" paragraph 4", "quote": "We analyzed data from 1410 individuals, including 208 patients with melanoma and 147 healthy controls, and 991 patients with colorectal cancer and 64 healthy controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:32209538"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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