Expression of genes related to lipid-handling may underlie the "obesity paradox" in melanoma: a public database-based approach.

BACKGROUND: Background. Genomic and transcriptomic data publicly available in huge searchable databases allow to address specific medical issues in thousand patients. Many studies highlight the role lipids play in cancer setup and progression and report nutritional interventions aimed at improving prognosis and survival. Therefore, increasing interest is given to the role fat intake may play. A relation between body mass and survival in cancer patients is known, as well as the association between high-fat diet and increased cancer risk. In different cancers, such as colorectal cancer, obesity and fat intake are known to induce setup and progression. On the contrary, in melanoma patients under therapy, an increased body mass index unexpectedly acts as a protective factor rather than as a risk factor, a phenomenon known as "obesity paradox". OBJECTIVE: Objectives. Identifying the molecular machinery underlining the "obesity paradox" may indicate new effective strategies to reduce risk factors and improve protective approaches. METHODS: Methods. In order to clarify, at least in part, the genes potentially involved, we investigated the expression values of lipid-related genes in melanoma patients and in colorectal cancer patients, in a total of 2990 patients from 3 public databases, namely Ist Online, GEO, Oncomine in a three-consecutive validation steps procedure. More in details, 1410 individuals were analyzed in Ist Online database (208 melanoma patients and 147 healthy controls, 991 colorectal cancer patients and 64 healthy colorectal controls). In addition, 45 melanoma, 18 nevi and 7 healthy skin biopsies were analyzed in an independent database (GEO) to validate Ist Online data. Finally, in Oncomine database 318 melanoma patients vs 312 controls and 435 colorectal cancer vs 445 controls were analyzed. RESULTS: Results. In the first and second database investigated, melanoma patients consistently show significantly (p< 0.0001) lower expression levels of 4 genes as compared to healthy controls, namely: CD36, MARCO, FABP4, FABP7. Such strong reduction is not observed in colorectal cancer patients. An additional analysis was carried out in DNA-TCGA dataset from Oncomine database, further validating CD36 and FABP4. CONCLUSIONS: Conclusions. We hypothesize that the observed lower expression of such genes may reduce fat-internalization and therefore make melanoma patients less sensible to high fat dietary intake, explaining at least in part the obesity paradox observed in melanoma patients. CLINICALTRIAL: