Abstract
BackgroundPublicly available genomic and transcriptomic data in searchable databases allow researchers to investigate specific medical issues in thousands of patients. 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.ObjectiveWe 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.MethodsIn 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.ResultsIn 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.ConclusionsThe 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.
Highlights
Genomic, transcriptomic, and proteomic data from several thousand patients and corresponding healthy controls are publicly available on the internet, for many different pathologies, including different types of cancers
We indicated our genes of interest (CD36, macrophage receptor with collagenous structure (MARCO), FABP1, FABP2, FABP3, FABP4, FABP6, or FABP7) as the first gene and used a known housekeeping gene, beta-2 microglobulin (B2M), as the reference gene; it should be noted that the expression values of the first gene are independent from the reference gene and the values do not change if a different reference gene is chosen
Gene expression of CD36, MARCO, and various fatty acid–binding proteins (FABPs) isoforms in 355 patients (208 patients with melanoma versus 147 healthy skin controls) was analyzed, according to the transcriptome expression data reported in the IST Online database
Summary
Transcriptomic, and proteomic data from several thousand patients and corresponding healthy controls are publicly available on the internet, for many different pathologies, including different types of cancers. 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. Results: In the first and second database investigated (IST Online and GEO, respectively), patients with melanoma consistently showed significantly (P
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