Proteomic analysis of lung adenocarcinoma: identification of a highly expressed set of proteins in tumors.
OBJECTIVE
The goal of this study was to identify potential protein markers in lung adenocarcinomas.


METHODS
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), beta1,4-galactosyltransferase, cytosolic inorganic pyrophosphatase, glucose-regulated M(r) 58,000 protein, glutathione-S-transferase M4, prolyl 4-hydroxylase beta 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 M(r) 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.
Section of General Thoracic Surgery, Departments of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Guoan
G
Chen
Tarek G
TG
Gharib
Chiang-Ching
CC
Huang
Dafydd G
DG
Thomas
Kerby A
KA
Shedden
Jeremy M G
JM
Taylor
Sharon L R
SL
Kardia
David E
DE
Misek
Thomas J
TJ
Giordano
Mark D
MD
Iannettoni
Mark B
MB
Orringer
Samir M
SM
Hanash
David G
DG
Beer
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms; D020543:Proteome / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D020543:Proteome; D012333:RNA, Messenger; D012334:RNA, Neoplasm