Five genes influenced by obesity may contribute to the development of thyroid cancer through the regulation of insulin levels

Abstract

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.

Bioinformatics analysis identified shared differentially expressed genes as potential biomarkers for Hashimoto's thyroiditis-related papillary thyroid cancer

“…In addition, LTF gene expression is decreased in thyroid cancer patients [46]. These results are consistent with the findings of our study.…”

“…Using indirect immunofluorescence, Afeltra's group identified anti-lactoferrin antibodies in 2 of 11 (18.1%) HT cases 45 . In addition, LTF gene expression is decreased in thyroid cancer patients 46 . These results are consistent with the findings of our study.…”

The association of obesity with thyroid carcinoma risk

“…Increased systemic adiposity can contribute to steatosis in thyroid follicular cells and may result in primary hypothyroidism in patients with obesity 40 . The expression of five obesity genes (TC FABP4, CFD, GHR, TNFRSF11B, and LTF) is significantly decreased in patients with TC, promoting TC progression and playing a role in the etiology of TC 62 . Obesity‐associated genetic variants rs8047395 and rs8044769 were positively associated with an increased risk of TC in the matched case‐control study 22 …”