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

Hoon Young Suh,Jin Chul Paeng,Hongyoon Choi,June-Key Chung,Gi Jeong Cheon,Keon Wook Kang

doi:10.1186/s12885-019-6482-7

Hoon Young Suh, Jin Chul Paeng + Show 4 more

Open Access

https://doi.org/10.1186/s12885-019-6482-7

Copy DOI

Abstract

BackgroundThe 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).MethodsWe 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.ResultsIn 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.ConclusionsAs 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.Trial registrationNot applicable.

Highlights

The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging
The integrative analysis of iodine and glucose metabolism based on the systemic gene expression data is needed for the molecular background of imaging and therapy of thyroid cancer
To evaluate the association between tumor differentiation and glucose metabolism in the thyroid cancer, we used two cohorts, papillary thyroid cancer (PTC) samples of The Cancer Genome Atlas (TCGA) and poorly differentiated thyroid cancer (PDTC)/ anaplastic thyroid cancer (ATC) samples obtained by Gene Expression Omnibus (GEO) (GSE76039)

Summary

Introduction

The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. The dedifferentiation according to BRAF mutation leads to increased glucose consumption of cancer cells [1], which is supported by the finding that PTC with BRAF mutation showed a trend of more FDG avidity [7] In spite of these crosssectional studies using imaging, there is a lack of comprehensive understanding of the association between tumor glucose metabolism, differentiation and BRAF mutation. Recent comprehensive analyses using generation sequencing have revealed new integrative molecular subtypes as well as cancer drivers [8] In this regard, the integrative analysis of iodine and glucose metabolism based on the systemic gene expression data is needed for the molecular background of imaging and therapy of thyroid cancer

Objectives

Methods

Results

Discussion

Conclusion