PMID- 25590838
OWN - NLM
STAT- MEDLINE
DCOM- 20150410
LR  - 20220316
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 94
IP  - 2
DP  - 2015 Jan
TI  - A metabolic phenotype based on mitochondrial ribosomal protein expression as a 
      predictor of lymph node metastasis in papillary thyroid carcinoma.
PG  - e380
LID - 10.1097/MD.0000000000000380 [doi]
LID - e380
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 alpha 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.
FAU - Lee, Jandee
AU  - Lee J
AD  - From the Department of Surgery (JL, M-YS, CRL, S-WK, JJJ, K-HN, WYC); and the 
      Department of Internal Medicine (SJ, CRK, DYS, EJL, YSJ), Severance Hospital, 
      Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
FAU - Seol, Mi-Youn
AU  - Seol MY
FAU - Jeong, Seonhyang
AU  - Jeong S
FAU - Lee, Cho Rok
AU  - Lee CR
FAU - Ku, Cheol Ryong
AU  - Ku CR
FAU - Kang, Sang-Wook
AU  - Kang SW
FAU - Jeong, Jong Ju
AU  - Jeong JJ
FAU - Shin, Dong Yeob
AU  - Shin DY
FAU - Nam, Kee-Hyun
AU  - Nam KH
FAU - Lee, Eun Jig
AU  - Lee EJ
FAU - Chung, Woong Youn
AU  - Chung WY
FAU - Jo, Young Suk
AU  - Jo YS
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (mitochondrial ribosomal protein L44, human)
SB  - IM
EIN - Medicine (Baltimore). 2015 Feb;94(8):1
EIN - Medicine (Baltimore). 2015 Feb;94(8):1. PMID: 25803366
MH  - Biomarkers, Tumor/genetics
MH  - *Carcinoma/genetics/metabolism/pathology
MH  - Carcinoma, Papillary
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Cellular Reprogramming
MH  - Confidence Intervals
MH  - Cross-Sectional Studies
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Lymph Nodes/*pathology
MH  - *Lymphatic Metastasis/diagnosis/genetics
MH  - Male
MH  - Middle Aged
MH  - Mitochondrial Proteins/*genetics
MH  - Multivariate Analysis
MH  - Neck
MH  - *Oxidative Phosphorylation
MH  - Prognosis
MH  - RNA, Messenger
MH  - Republic of Korea
MH  - Ribosomal Proteins/*genetics
MH  - Thyroid Cancer, Papillary
MH  - *Thyroid Neoplasms/genetics/metabolism/pathology
PMC - PMC4602546
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2015/01/16 06:00
MHDA- 2015/04/11 06:00
PMCR- 2015/01/16
CRDT- 2015/01/16 06:00
PHST- 2015/01/16 06:00 [entrez]
PHST- 2015/01/16 06:00 [pubmed]
PHST- 2015/04/11 06:00 [medline]
PHST- 2015/01/16 00:00 [pmc-release]
AID - 00005792-201501020-00008 [pii]
AID - 10.1097/MD.0000000000000380 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2015 Jan;94(2):e380. doi: 10.1097/MD.0000000000000380.