A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma

Jandee Lee, Mi Youn Seol, Seonhyang Jeong, Cho Rok Lee, Cheol Ryong Ku, Sang Wook Kang, Jong Ju Jeong, Dong Yeob Shin, Kee Hyun Nam, Eunjig Lee, Woong Youn Chung, Young Suk Jo

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Abstract

Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized.The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations.Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features.GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P<0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P<0.001). Furthermore, multivariate analysis clearly indicated that expression of MRPL44 is associated with an increased risk of lateral neck LNM (odds ratio 9.267, 95% confidence interval 1.852-46.371, P=0.007).MRPL44 expression may be a representative marker of metabolic phenotype according to OxPhos amount and a useful predictor of LNM.

Original languageEnglish
Pages (from-to)e380
JournalMedicine (United States)
Volume94
Issue number2
DOIs
Publication statusPublished - 2015 Jan 2

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Ribosomal Proteins
Mitochondrial Proteins
Oxidative Phosphorylation
Lymph Nodes
Neoplasm Metastasis
Phenotype
Thyroid Neoplasms
Messenger RNA
Thyroid Gland
Genes
Dilatation and Curettage
Factor IX
Ubiquinone
Mitochondrial Genes
Succinate Dehydrogenase
Papillary Thyroid cancer
Gene Regulatory Networks
Cytochromes
Oxygen Consumption
NAD

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Lee, Jandee ; Seol, Mi Youn ; Jeong, Seonhyang ; Lee, Cho Rok ; Ku, Cheol Ryong ; Kang, Sang Wook ; Jeong, Jong Ju ; Shin, Dong Yeob ; Nam, Kee Hyun ; Lee, Eunjig ; Chung, Woong Youn ; Jo, Young Suk. / A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma. In: Medicine (United States). 2015 ; Vol. 94, No. 2. pp. e380.
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abstract = "Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized.The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations.Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features.GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3{\%}) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P<0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P<0.001). Furthermore, multivariate analysis clearly indicated that expression of MRPL44 is associated with an increased risk of lateral neck LNM (odds ratio 9.267, 95{\%} confidence interval 1.852-46.371, P=0.007).MRPL44 expression may be a representative marker of metabolic phenotype according to OxPhos amount and a useful predictor of LNM.",
author = "Jandee Lee and Seol, {Mi Youn} and Seonhyang Jeong and Lee, {Cho Rok} and Ku, {Cheol Ryong} and Kang, {Sang Wook} and Jeong, {Jong Ju} and Shin, {Dong Yeob} and Nam, {Kee Hyun} and Eunjig Lee and Chung, {Woong Youn} and Jo, {Young Suk}",
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A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma. / Lee, Jandee; Seol, Mi Youn; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang Wook; Jeong, Jong Ju; Shin, Dong Yeob; Nam, Kee Hyun; Lee, Eunjig; Chung, Woong Youn; Jo, Young Suk.

In: Medicine (United States), Vol. 94, No. 2, 02.01.2015, p. e380.

Research output: Contribution to journalArticle

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T1 - A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma

AU - Lee, Jandee

AU - Seol, Mi Youn

AU - Jeong, Seonhyang

AU - Lee, Cho Rok

AU - Ku, Cheol Ryong

AU - Kang, Sang Wook

AU - Jeong, Jong Ju

AU - Shin, Dong Yeob

AU - Nam, Kee Hyun

AU - Lee, Eunjig

AU - Chung, Woong Youn

AU - Jo, Young Suk

PY - 2015/1/2

Y1 - 2015/1/2

N2 - Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized.The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations.Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features.GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P<0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P<0.001). Furthermore, multivariate analysis clearly indicated that expression of MRPL44 is associated with an increased risk of lateral neck LNM (odds ratio 9.267, 95% confidence interval 1.852-46.371, P=0.007).MRPL44 expression may be a representative marker of metabolic phenotype according to OxPhos amount and a useful predictor of LNM.

AB - Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized.The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations.Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features.GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P<0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P<0.001). Furthermore, multivariate analysis clearly indicated that expression of MRPL44 is associated with an increased risk of lateral neck LNM (odds ratio 9.267, 95% confidence interval 1.852-46.371, P=0.007).MRPL44 expression may be a representative marker of metabolic phenotype according to OxPhos amount and a useful predictor of LNM.

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