Expression of Interleukin-1 Receptor–Associated Kinase-1 in Non–Small Cell Lung Carcinoma and Preneoplastic Lesions
Open Access
- 1 January 2010
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 16 (1), 34-44
- https://doi.org/10.1158/1078-0432.ccr-09-0650
Abstract
Purpose: To identify the pattern of interleukin-1 receptor–associated kinase (IRAK-1) protein expression in non–small cell lung carcinoma (NSCLC) and corresponding preneoplastic lesions. Experimental Design: Archived tissue from NSCLC (adenocarcinoma and squamous cell carcinoma; n = 306) and adjacent bronchial epithelial specimens (n = 315) were analyzed for the immunohistochemical expression of IRAK-1, and the findings were correlated with patients' clinicopathologic features. Furthermore, we investigated the correlation between IRAK-1 expression and expression of NF-κB and IL-1α in tumor specimens. Results: NSCLC tumors showed significantly higher cytoplasmic and lower nuclear IRAK-1 expression than normal epithelium. Squamous dysplasias had significantly higher cytoplasmic IRAK-1 expression than normal epithelium. In tumors, a significant positive correlation was detected between IRAK-1 expression (nuclear and cytoplasmic; P = 0.011) and IL-1α cytoplasmic expression (P < 0.0001). The correlation between the expression of the markers and patients' clinicopathologic features varied according to tumor histologic type and sex. High IRAK-1 cytoplasmic expression correlated with worse recurrence-free survival in women with NSCLC [hazard ratio (HR), 2.204; P = 0.033], but not in men. In adenocarcinoma, combined low level of expression of nuclear IRAK-1 and NF-κB correlated significantly with worse overall (HR, 2.485; P = 0.007) and recurrence-free (HR, 3.058; P = 0.006) survivals in stage I/II patients. Conclusions: IRAK-1 is frequently expressed in NSCLC tissue specimens, and this expression is an early phenomenon in the sequential development of lung cancer. IRAK-1 is a novel inflammation-related marker and a potential target for lung cancer chemopreventive strategies. Clin Cancer Res; 16(1); 34–44Keywords
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