Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer.
OBJECTIVE
Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancer-testis gene expression occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non-small cell lung cancer (NSCLC).


METHODS
Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome.


RESULTS
At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1 and MAGE-A3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung.


CONCLUSIONS
Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.
Gure
Ali O
AO
Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA. agure@med.cornell.edu
Chua
Ramon
R
Williamson
Barbara
B
Gonen
Mithat
M
Ferrera
Cathy A
CA
Gnjatic
Sacha
S
Ritter
Gerd
G
Simpson
Andrew J G
AJ
Chen
Yao-T
YT
Old
Lloyd J
LJ
Altorki
Nasser K
NK
D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013737:Testis / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D008565:Membrane Proteins