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Liver X Receptor ? Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer.

ABSTRACT: BACKGROUND:Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features. METHODS:Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXR? expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort. RESULTS:In contrast to low expression of LXR?, LXR? was highly expressed in thyroid cancer compared to the other types of human cancers. High LXR? expression was correlated with the expression of LXR? transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXR? expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXR? expression was coordinately related to ribosome-related gene sets. CONCLUSION:The mechanistic link between LXR? and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

SUBMITTER: Jeong S

PROVIDER: S-EPMC7520597 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer.

Jeong Seonhyang S Kim In-Kyu IK Kim Hyunji H Choi Moon Jung MJ Lee Jandee J Jo Young Suk YS

Endocrinology and metabolism (Seoul, Korea) 20200820 3

<h4>Background</h4>Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features.<h4>Methods</h4>Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets re ...[more]

PMID: 32814418

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Project description:Aberrant expression of Cancer Osaka Thyroid Oncogene mitogen-activated protein kinase kinase kinase 8 (COT) (MAP3K8) is a driver of resistance to B-RAF inhibition. However, the de novo expression and clinical implications of COT in papillary thyroid cancer (PTC) have not been investigated.The aim of this study is to investigate the expression of A-, B-, C-RAF, and COT in PTC (n?=?167) and analyze the clinical implications of aberrant expression of these genes.Quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC) were performed on primary thyroid cancers. Expression of COT was compared with clinicopathological characteristics including recurrence-free survival. Datasets from public repository (NCBI) were subjected to Gene Set Enrichment Analysis (GSEA).qPCR data showed that the relative mRNA expression of A-, B-, C-RAF and COT of PTC were higher than normal tissues (all P?<?0.01). In addition, the expression of COT mRNA in PTC showed positive correlation with A- (r?=?0.4083, P?<?0.001), B- (r?=?0.2773, P?=?0.0003), and C-RAF (r?=?0.5954, P?<?0.001). The mRNA expressions of A-, B,- and C-RAF were also correlated with each other (all P?<?0.001). In IHC, the staining intensities of B-RAF and COT were higher in PTC than in normal tissue (P?<?0.001). Interestingly, moderate-to-strong staining intensities of B-RAF and COT were more frequent in B-RAF-positive PTC (P?<?0.001, P?=?0.013, respectively). In addition, aberrant expression of COT was related to old age at initial diagnosis (P?=?0.045) and higher recurrence rate (P?=?0.025). In multivariate analysis, tumor recurrence was persistently associated with moderate-to-strong staining of COT after adjusting for age, sex, extrathyroidal extension, multifocality, T-stage, N-stage, TNM stage, and B-RAF mutation (odds ratio, 4.662; 95% confidence interval 1.066?-?21.609; P?=?0.045). Moreover, moderate-to-strong COT expression in PTC was associated with shorter recurrence-free survival (mean follow-up duration, 14.2?±?4.1 years; P?=?0.0403). GSEA indicated that gene sets related to B-RAF-RAS (P?<?0.0001, false discovery rate [FDR] q-value?=?0.000) and thyroid differentiation (P?=?0.048, FDR q-value?=?0.05) scores were enriched in lower COT expression group and gene sets such as T-cell receptor signaling pathway and Toll-like receptor signaling pathway are coordinately upregulated in higher COT expression group (both, P?<?0.0001, FDR q-value?=?0.000).Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC.

Dataset Information

Liver X Receptor ? Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer.

Publications

Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer.

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