Expression of Genes Related to Lipid Handling and the Obesity Paradox in Melanoma: Database Analysis
Expression of Genes Related to Lipid Handling and the Obesity Paradox in Melanoma: Database Analysis
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DOI：
10.2196/16974
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发表时间：
2020-05-19
期刊：
影响因子：
2.8
通讯作者：
Facchiano, Antonio
中科院分区：
文献类型：
--
作者：
Giampietri, Claudia;Tomaipitinca, Luana;Facchiano, Antonio
背景：可搜索数据库中公开的基因组和转录组数据使研究人员能够调查数千名患者的特定医疗问题。许多研究强调了脂质在癌症发生和进展中的作用，并报告了旨在改善预后和生存的营养干预措施。因此，人们越来越关注脂肪摄入在癌症中可能发挥的作用。众所周知，BMI 与癌症患者的生存率之间存在相关性，并且高脂肪饮食与癌症风险增加之间存在关联。在某些癌症中，例如结直肠癌，肥胖和高脂肪摄入会增加癌症发生和进展的风险。相反，在接受黑色素瘤治疗的患者中，较高的 BMI 出人意料地充当了保护因素，而不是危险因素；这种现象被称为肥胖悖论。目的：我们旨在确定肥胖悖论背后的分子机制，期望这可以为减少危险因素和改进保护方法提供新的有效策略。方法：为了确定可能参与这一过程的基因，我们研究了黑色素瘤或结直肠癌患者中脂质相关基因的表达值。我们在涉及 3 个连续验证步骤的分析中使用了来自 3 个公共数据库（IST [In Silico Transcriptomics] Online、GEO [Gene Expression Omnibus] 和 Oncomine）的 2990 名患者的可用数据。在 IST Online 数据库中分析了该组中 1410 名个体的数据（208 名黑色素瘤患者和 147 名健康对照，以及 991 名结直肠癌患者和 64 名健康对照）。此外，我们还在另一个数据库 GEO 中分析了 45 个黑色素瘤、18 个痣和 7 个健康皮肤活检样本，以验证 IST Online 数据。最后，使用 Oncomine 数据库对 318 名黑色素瘤患者（312 名对照）和 435 名结直肠癌患者（445 名对照）进行了分析。结果：在调查的第一个和第二个数据库（分别为 IST Online 和 GEO）中，黑色素瘤患者始终表现出显着（P
Background: Publicly 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.Objective: 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.Methods: 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.Results: In the first and second database investigated (IST Online and GEO, respectively), patients with melanoma consistently showed significantly (P