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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  ;  Eun Jig Lee  ;  Woong Youn Chung  ;  Young Suk Jo 
 MEDICINE, Vol.94(2) : 380, 2015 
Journal Title
Issue Date
Biomarkers, Tumor/genetics ; Carcinoma*/genetics ; Carcinoma*/metabolism ; Carcinoma*/pathology ; Carcinoma, Papillary ; Cell Transformation, Neoplastic/genetics* ; Cellular Reprogramming ; Confidence Intervals ; Cross-Sectional Studies ; Female ; Gene Expression Profiling ; Humans ; Lymph Nodes/pathology* ; Lymphatic Metastasis*/diagnosis ; Lymphatic Metastasis*/genetics ; Male ; Middle Aged ; Mitochondrial Proteins/genetics* ; Multivariate Analysis ; Neck ; Oxidative Phosphorylation* ; Prognosis ; RNA, Messenger ; Republic of Korea ; Ribosomal Proteins/genetics* ; Thyroid Neoplasms*/genetics ; Thyroid Neoplasms*/metabolism ; Thyroid Neoplasms*/pathology
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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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Sang Wook(강상욱) ORCID logo https://orcid.org/0000-0001-5355-833X
Ku, Cheol Ryong(구철룡) ORCID logo https://orcid.org/0000-0001-8693-9630
Nam, Kee Hyun(남기현) ORCID logo https://orcid.org/0000-0002-6852-1190
Seol, Mi Youn(설미연)
Shin, Dong Yeob(신동엽) ORCID logo https://orcid.org/0000-0003-1048-7978
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Lee, Jan Dee(이잔디) ORCID logo https://orcid.org/0000-0003-4090-0049
Lee, Cho Rok(이초록) ORCID logo https://orcid.org/0000-0001-7848-3709
Jeong, Seonhyang(정선향) ORCID logo https://orcid.org/0000-0002-5549-9182
Chung, Woong Youn(정웅윤)
Jeong, Jong Ju(정종주) ORCID logo https://orcid.org/0000-0002-4155-6035
Jo, Young Suk(조영석) ORCID logo https://orcid.org/0000-0001-9926-8389
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