PMID- 14963017
OWN - NLM
STAT- MEDLINE
DCOM- 20040803
LR  - 20151119
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 25
IP  - 7
DP  - 2004 Jul
TI  - The bioenergetic signature of lung adenocarcinomas is a molecular marker of 
      cancer diagnosis and prognosis.
PG  - 1157-63
AB  - The aim of this study was to investigate the mitochondrial bioenergetic signature 
      of lung adenocarcinomas as a prognostic marker of cancer progression. For this 
      purpose, a series of 90 lung adenocarcinomas and 10 uninvolved lung samples were 
      examined for quantitative differences in protein expression using two-dimensional 
      polyacrylamide gel electrophoresis. The beta subunit of the mitochondrial 
      H(+)-ATP synthase (beta-F1-ATPase) and heat shock protein 60 (Hsp 60), and the 
      glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH), used to define the 
      bioenergetic cellular (BEC) index, were identified using mass spectrometry and 
      specific antibodies. Correlations of the expression level of the protein markers 
      and of the BEC index were established with the clinicopathological information of 
      the tumors and the follow-up data of the patients. The expression of 
      beta-F1-ATPase is significantly reduced in lung adenocarcinomas in the absence of 
      significant changes in the expression of Hsp 60 and of a major GAPDH isoform. 
      Cross-validation analysis using the beta-F1-ATPase/Hsp 60 ratio and GAPDH 
      expression as predictor variables revealed a classification sensitivity of 97.3%. 
      The beta-F1-ATPase/Hsp 60 ratio is significantly higher in well differentiated 
      and bronchioloalveolar tumors than in moderate or poorly differentiated and in 
      bronchial-derived tumors. The BEC index of T1 tumors was significantly higher 
      than that of T2 tumors. Likewise, stage IA tumors had a higher BEC index than 
      stage IB tumors. Kaplan-Meier survival analysis using the BEC index as predictor 
      of survival revealed that within tumors of the same size or stage I or with no 
      lymph node metastasis (N0) the patients bearing 'low' BEC index tumors had a 
      significant worse prognosis. We conclude that the bioenergetic signature of lung 
      adenocarcinomas is altered, further providing a relevant marker for the diagnosis 
      and classification of lung adenocarcinomas, and for the prognosis of lung cancer 
      patients.
FAU - Cuezva, Jose M
AU  - Cuezva JM
AD  - Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, 
      Universidad Autonoma de Madrid, E-28049 Madrid, Spain. jmcuezva@cbm.uam.es
FAU - Chen, Guoan
AU  - Chen G
FAU - Alonso, Andres M
AU  - Alonso AM
FAU - Isidoro, Antonio
AU  - Isidoro A
FAU - Misek, David E
AU  - Misek DE
FAU - Hanash, Samir M
AU  - Hanash SM
FAU - Beer, David G
AU  - Beer DG
LA  - eng
GR  - U19 CA-85953/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040212
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Biomarkers)
RN  - 0 (Chaperonin 60)
RN  - 0 (Isoenzymes)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
SB  - IM
MH  - Adenocarcinoma/*diagnosis/metabolism
MH  - *Biomarkers
MH  - Chaperonin 60/metabolism
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Energy Metabolism/*physiology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/genetics/metabolism
MH  - Humans
MH  - Isoenzymes/genetics/metabolism
MH  - Lung Neoplasms/*diagnosis/metabolism
MH  - Mitochondrial Proton-Translocating ATPases/metabolism
MH  - Time Factors
EDAT- 2004/02/14 05:00
MHDA- 2004/08/04 05:00
CRDT- 2004/02/14 05:00
PHST- 2004/02/14 05:00 [pubmed]
PHST- 2004/08/04 05:00 [medline]
PHST- 2004/02/14 05:00 [entrez]
AID - bgh113 [pii]
AID - 10.1093/carcin/bgh113 [doi]
PST - ppublish
SO  - Carcinogenesis. 2004 Jul;25(7):1157-63. doi: 10.1093/carcin/bgh113. Epub 2004 Feb 
      12.