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Clinical Cancer Research Vol. 8, 2298-2305, July 2002
© 2002 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Proteomic Analysis of Lung Adenocarcinoma

Identification of a Highly Expressed Set of Proteins in Tumors1

Guoan Chen, Tarek G. Gharib, Chiang-Ching Huang, Dafydd G. Thomas, Kerby A. Shedden, Jeremy M. G. Taylor, Sharon L. R. Kardia, David E. Misek, Thomas J. Giordano, Mark D. Iannettoni, Mark B. Orringer, Samir M. Hanash and David G. Beer2

Section of General Thoracic Surgery, Departments of Surgery [G. C., T. G. G., M. D. I., M. B. O., D. G. B.], Biostatistics [C-C. H., K. A. S., J. M. G. T.], Pathology [T. J. G., D. G. T.], Pediatrics [D. E. M., S. M. H.], and Epidemiology [S. L. R. K.], University of Michigan, Ann Arbor, Michigan 48109

Purpose: The goal of this study was to identify potential protein markers in lung adenocarcinomas.

Experimental Design: A series of 93 lung adenocarcinomas (64 stage I and 29 stage III) and 10 uninvolved lung samples were examined for quantitative differences in protein expression using two-dimensional PAGE. Candidate proteins were identified using matrix-assisted laser desorption/ionization mass spectrometry or peptide sequencing. The levels of the individual isoforms of nine proteins found to be overexpressed in the lung tumors were examined. Potential mechanisms for overexpression were examined by comparing mRNA expression levels, assessed using oligonucleotide arrays, to the protein values in the same samples.

Results: Antioxidant enzyme AOE372, ATP synthase subunit d (ATP5D), ß1,4-galactosyltransferase, cytosolic inorganic pyrophosphatase, glucose-regulated Mr 58,000 protein, glutathione-S-transferase M4, prolyl 4-hydroxylase ß subunit, triosephosphate isomerase, and ubiquitin thiolesterase (UCHL1) were identified as being significantly overexpressed in lung adenocarcinomas. The expression of these proteins was increased from 1.4- to 10.6-fold as compared with uninvolved lung tissue. The expression of the individual protein isoforms was correlated with 10 clinicopathological variables as well as with each gene’s mRNA level in the same sample. Both isoforms of glucose-regulated Mr 58,000 protein were found to be significantly correlated with their mRNA expression profiles (P < 0.05), indicating that increased transcription likely underlies the increased expression of these proteins.

Conclusions: Two-dimensional PAGE and mass spectrometry can identify proteins showing increased expression in lung adenocarcinoma. The association of specific isoforms of these proteins with clinical variables and understanding the regulation of their expression will aid in determination of their potential use as biomarkers in this cancer.




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Copyright © 2002 by the American Association for Cancer Research.