Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue.
Associations between clinical outcome of cancer patients and the gene expression signature in primary tumors at time of diagnosis have been reported. To test whether gene expression patterns in noninvolved lung tissue might correlate with clinical stage in lung adenocarcinoma (ADCA) patients, we compared the transcriptome of noninvolved lung samples from 60 ADCA smoker patients of clinical stage I versus 60 patients with stage>I. Quantitative PCR of 10 genes with the most significant differential expression confirmed the statistical association with clinical stage in eight genes, six of which were downregulated in high-stage patients. Five of these six genes were also downregulated in lung ADCA tissue as compared to noninvolved tissue. Studies in vitro indicated that four of the genes (SLC14A1, SMAD6, TMEM100 and TXNIP) inhibited colony formation of lung cancer cell lines transfected to overexpress the genes, suggesting their potential tumor-suppressor activity. Our findings suggest that individual variations in the transcriptional profile of noninvolved lung tissue may reflect the lung ADCA patient's predisposition to tumor aggressiveness.
Department of Predictive and Preventive Medicine, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy.
Elisa
E
Frullanti
Francesca
F
Colombo
Felicia S
FS
Falvella
Antonella
A
Galvan
Sara
S
Noci
Loris
L
De Cecco
Matteo
M
Incarbone
Marco
M
Alloisio
Luigi
L
Santambrogio
Mario
M
Nosotti
Davide
D
Tosi
Ugo
U
Pastorino
Tommaso A
TA
Dragani
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / 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* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D014408:Biomarkers, Tumor; D012333:RNA, Messenger