| Summary: | Previous studies indicate that obesity is an important contributor to the proceeding of thyroid cancer (TC) with limited knowledge of the underlying mechanism. Here, we hypothesize that molecules affected by obesity may play roles in the development of TC. To test the hypothesis above, we first conducted a large-scale literature-based data mining to identify genes influenced by obesity and genes related to TC. Then, a mega-analysis was conducted to study the expression changes of the obesity-specific genes in the case of TC, using 16 independent TC array-expression datasets (783 TC cases and 439 healthy controls). After that, pathway analysis was performed to explore the functional profile of the selected target genes and their potential connections with TC. We identified 1,036 genes associated with TC and 534 regulated by obesity, demonstrating a significant overlap (N = 176, p-value = 4.07e−112). Five out of the 358 obesity-specific genes, FABP4, CFD, GHR, TNFRSF11B, and LTF, presented significantly decreased expression in TC patients (LFC<−1.44; and p-value < 1e−7). Multiple literature-based pathways were identified where obesity could promote the pathologic development of TC through the regulation of these five genes and INS levels. The five obesity genes uncovered could be novel genes that play roles in the etiology of TC through the modulation of INS levels.
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