Differentially expressed apoptotic genes in early stage lung adenocarcinoma predicted by expression profiling.
OBJECTIVE
In undiseased lung epithelial cells, apoptosis is an evolutionarily conserved and genetically regulated form of cell suicide which plays an important role in development and in the maintenance of tissue homeostasis. Neoplastic lung cells develop the ability to deregulate growth by alterations in these genes which control apoptosis. Genomic profiling was used to compare gene expression levels in early stage lung adenocarcinomas and nonneoplastic pulmonary tissue in order to comprehensively identify alterations in the process of apoptosis.


METHODS
RNA extracted from node negative, poorly differentiated lung adenocarcinomas (15 patients) and nonneoplastic pulmonary tissue (5 patients) was hybridized to oligonucleotide microarray filters containing 44,363 genes. Ontological classification was used to extract genes involved with apoptosis. Further analysis discovered a subset of differentially expressed genes for further study.


RESULTS
Of the 308 apoptotic genes on the microarray filters, 24 genes were predicted to be differentially expressed in lung adenocarcinomas. Alterations in several genes (i.e., Akt, BcL-xL, PTEN, FAS) are consistent with the literature. We also identified 10 novel genes that have not been described in nonsmall cell lung cancer (i.e., RIP, Caspase 1, PDK-1).


CONCLUSIONS
These results identified several potential apoptotic genes altered in lung cancer.
Singhal
Sunil
S
Section of General Thoracic Surgery, Division of Cardiothoracic Surgery, Department of Surgery, University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania USA.
Amin
Kunjlata M
KM
Kruklitis
Robert
R
Marshall
M Blair
MB
Kucharczuk
John C
JC
DeLong
Peter
P
Litzky
Leslie A
LA
Kaiser
Larry R
LR
Albelda
Steven M
SM
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
D009363:Neoplasm Proteins; D012333:RNA, Messenger