The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis

José M. Cuezva; Guoan Chen; Andrés M. Alonso; Antonio Isidoro; David E. Misek; Samir M. Hanash; David G. Beer

doi:10.1093/carcin/bgh113

The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis

José M. Cuezva, Guoan Chen, Andrés M. Alonso, Antonio Isidoro, David E. Misek, Samir M. Hanash, David G. Beer

Research output: Contribution to journal › Review article › peer-review

132 Scopus citations

Abstract

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 β subunit of the mitochondrial H⁺-ATP synthase (β-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 β-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 β-F1-ATPase/Hsp 60 ratio and GAPDH expression as predictor variables revealed a classification sensitivity of 97.3%. The β-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.

Original language	English (US)
Pages (from-to)	1157-1163
Number of pages	7
Journal	Carcinogenesis
Volume	25
Issue number	7
DOIs	https://doi.org/10.1093/carcin/bgh113
State	Published - Jul 2004
Externally published	Yes

ASJC Scopus subject areas

Cancer Research

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10.1093/carcin/bgh113

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@article{f9509b9a91d2475cb10038099f27680d,

title = "The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis",

abstract = "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 β subunit of the mitochondrial H+-ATP synthase (β-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 β-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 β-F1-ATPase/Hsp 60 ratio and GAPDH expression as predictor variables revealed a classification sensitivity of 97.3%. The β-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.",

author = "Cuezva, {Jos{\'e} M.} and Guoan Chen and Alonso, {Andr{\'e}s M.} and Antonio Isidoro and Misek, {David E.} and Hanash, {Samir M.} and Beer, {David G.}",

note = "Funding Information: We thank Tarek G.Gharib for his excellent technical assistance and Drs Mark Orringer and Mark Iannettonni for providing lung tissue samples. A.I. is the recipient of a pre-doctoral fellowship from Fundaci{\'o}n Ram{\'o}n Areces. This work was supported by grants: 01/380 from Ministerio de Sanidad y Consumo and BMC2001-0710 from Ministerio de Ciencia y Tecnoloǵ{\~o}a to J.M.C. (Spain) and National Cancer Institute grant: U19 CA-85953 to S.M.H and D.G.B. (USA). The CBMSO receives an institutional grant from Fundaci{\'o}n Ram{\'o}n Areces.",

year = "2004",

month = jul,

doi = "10.1093/carcin/bgh113",

language = "English (US)",

volume = "25",

pages = "1157--1163",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "7",

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TY - JOUR

T1 - The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis

AU - Cuezva, José M.

AU - Chen, Guoan

AU - Alonso, Andrés M.

AU - Isidoro, Antonio

AU - Misek, David E.

AU - Hanash, Samir M.

AU - Beer, David G.

N1 - Funding Information: We thank Tarek G.Gharib for his excellent technical assistance and Drs Mark Orringer and Mark Iannettonni for providing lung tissue samples. A.I. is the recipient of a pre-doctoral fellowship from Fundación Ramón Areces. This work was supported by grants: 01/380 from Ministerio de Sanidad y Consumo and BMC2001-0710 from Ministerio de Ciencia y Tecnoloǵõa to J.M.C. (Spain) and National Cancer Institute grant: U19 CA-85953 to S.M.H and D.G.B. (USA). The CBMSO receives an institutional grant from Fundación Ramón Areces.

PY - 2004/7

Y1 - 2004/7

N2 - 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 β subunit of the mitochondrial H+-ATP synthase (β-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 β-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 β-F1-ATPase/Hsp 60 ratio and GAPDH expression as predictor variables revealed a classification sensitivity of 97.3%. The β-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.

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 β subunit of the mitochondrial H+-ATP synthase (β-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 β-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 β-F1-ATPase/Hsp 60 ratio and GAPDH expression as predictor variables revealed a classification sensitivity of 97.3%. The β-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.

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DO - 10.1093/carcin/bgh113

M3 - Review article

C2 - 14963017

AN - SCOPUS:3242753586

SN - 0143-3334

VL - 25

SP - 1157

EP - 1163

JO - Carcinogenesis

JF - Carcinogenesis

IS - 7

ER -

The bioenergetic signature of lung adenocarcinomas is a molecular marker of cancer diagnosis and prognosis

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