Use of microRNA expression levels to predict outcomes in resected stage I non-small cell lung cancer.
BACKGROUND
Despite undergoing curative resection, nearly a third of patients with stage I non-small cell lung cancer (NSCLC) die of recurrent disease. There are no reliable clinical or molecular predictors of relapse in patients with resected stage I NSCLC. Identifying patients at risk for relapse after surgical resection is one of the important challenges today. MicroRNAs (miRNAs) regulate hundreds of genes central to maintaining a cancer phenotype.


METHODS
In an exploratory study, we determined whether expression of six miRNAs (let-7a, miR-7, miR-21, miR-155, miR-210, and miR-221) previously reported to correlate with invasiveness or outcome in various human malignancies were associated with tumor recurrence in patients with resected stage I NSCLC. We measured expression of these miRNAs in formalin-fixed, paraffin-embedded tissue from both tumor and matched normal lung in a set of 46 patients with surgically resected T1 or T2 stage I NSCLC.


RESULTS
Averaged triplicate data showed that tumors which recurred had 0.14-fold lower miR-221 expression than those which did not recur (p = 0.0036). In addition, increased miR-221in tumor tissue when compared with adjacent normal appearing lung in the same patient also correlated with nonrecurrence (p = 0.0011). Parallel measurement of expression of selected downstream target genes regulated by miR-221, specifically, CDKN1B, CDKN1C, paralemmin-2, and CXCL12, showed a near significant (p = 0.0522) down-regulation of CDKN1C in tumors of patients with no recurrent disease, consistent with increased miR-221 activity in the same group.


CONCLUSIONS
If confirmed in prospective studies, miRNA expression in resected NSCLC could potentially identify those at high risk of relapse after surgery.
Duncavage
Eric
E
Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
Goodgame
Boone
B
Sezhiyan
Ananth
A
Govindan
Ramaswamy
R
Pfeifer
John
J
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D035683:MicroRNAs; C525709:MIR221, human