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Erschienen in:
01.09.2007
Aberrant Methylation of IL-12Rβ2 Gene in Lung Adenocarcinoma Cells Is Associated with Unfavorable Prognosis
Erschienen in: Annals of Surgical Oncology | Ausgabe 9/2007
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Background
Interleukin-12 receptor β2 (IL-12Rβ2) knock-out mice develop lung adenocarcinoma, and epigenetic silencing by CpG methylation leads to loss of this gene in B-cell malignancies. The aim of this study was to determine whether IL-12Rβ2 methylation is a common feature in human lung cancer.
Methods
We examined mRNA expression of IL-12Rβ2 in lung cancer cell lines, and normal bronchial, and tracheal epithelial cells using RT-PCR, and we examined the methylation status of IL-12Rβ2 in primary lung cancers.
Results
Loss of expression was found in 10 of 13 (77%) NSCLC cell lines, and 2 of 5 (40%) SCLC cell lines compared with normal bronchial or tracheal cells. Treatment of 11 expression-negative cell lines with a demethylating agent restored expression in all cases. Aberrant methylation status of IL-12Rβ2 gene was reversely concordant with its mRNA expression. IL-12Rβ2 methylation was detected in 96 of 230 primary NSCLCs (42%) and 3 of 6 primary SCLCs (50%). IL-12Rβ2 methylation correlated with poorer prognosis in lung adenocarcinomas (hazard ratio = 2.33, P = 0.0059).
Conclusions
We conclude that epigenetic silencing of IL-12Rβ2 is a frequent event in lung cancers. Aberrant methylation of this gene seems to be a useful predictor of long-term outcome for adenocarcinoma of the lung.