Comprehensive gene expression analysis for exploring the association between glucose metabolism and differentiation of thyroid cancer

Abstract

Background: The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is still lacking. We investigated the association between glucose metabolism and differentiation in advanced thyroid cancer as well as papillary thyroid cancer (PTC). Methods: We used RNA sequencing of 505 patients with PTC obtained from the Cancer Genome Archives and microarray data of poorly-differentiated and anaplastic thyroid cancer (PDTC/ATC). The signatures of GLUT and glycolysis were estimated to assess glucose metabolic profiles. The glucose metabolic profiles were associated with tumor differentiation score (TDS) and BRAFV600E mutation status. In addition, survival analysis of glucose metabolic profiles was performed for predicting recurrence-free survival. Results: In PTC, the glycolysis signature was positively correlated with TDS, while the GLUT signature was inversely correlated with TDS. These correlations were significantly stronger in the BRAFV600E negative group than the positive group. Meanwhile, both GLUT and glycolysis signatures were negatively correlated with TDS in advanced thyroid cancer. The high glycolysis signature was significantly associated with poor prognosis in PTC in spite of high TDS. The glucose metabolic profiles are intricately associated with tumor differentiation in PTC and PDTC/ATC. Conclusions: As glycolysis was an independent prognostic marker, we suggest that the glucose metabolism features of thyroid cancer could be another biological progression marker different from differentiation and provide clinical implications for risk stratification.

Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma

“…Previous studies have suggested that the SUVmax in BRAF V600E mutation bearing tumors was significantly higher than wild type variants in papillary thyroid cancer (PTC) [22,23]. It has also been shown that BRAF V600E mutation is significantly associated with the expression of GLUT-1 and glycolysis in thyroid cancer [24,25]. The prevalence of BRAF V600E mutation was 87.5% in this study which is consistent with other studies in poorly differentiated thyroid carcinoma and tall cell PTC [26][27][28].…”

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer

“…Thyroid cancers of aggressive clinical behavior have high glycolytic activity. This has a clear prognostic importance as originally demonstrated in a 2000 study published by the Memorial Sloan Kettering Cancer Center (MSKCC) group ( 57) and has been updated in a 2019 study incorporating additional molecular data (58). The FDG-RAI relationship is not a simple ''flip-flop'' phenomenon.…”

Study on the Antitumor Effect and Glycolysis of Andrographolide in Anaplastic Thyroid Carcinoma

“…It can be deduced from the present study that andrographolide might exert antitumor effects by inhibiting glycolysis in ATC cells. Based on the critical role of glycolysis in ATC development and treatment [24,26], the results of this study reinforce andrographolide as an effective candidate drug for the future treatment of ATC with great research significance and clinical transformation value.…”

“…Suh et al found that glycolysis is closely related to the differentiation of thyroid tumors. e glycolytic characteristics of thyroid cancer may be a prognostic indicator suggesting the risk stratification of thyroid cancer [24], and according to a study conducted by Hébrant et al, ATC showed a stronger glycolytic performance, which suggested that the significance and value of glycolysis in ATC are more important than those in PTC [25]. Meanwhile, studies have shown that inhibiting glycolysis in ATC cells can make ATC cells more sensitive to radiotherapy and chemotherapy [26,27].…”