Expression of Interleukin-1 Receptor-Associated Kinase-1 in Non-Small Cell Lung Carcinoma and Preneoplastic Lesions

被引:33
作者
Behrens, Carmen [2 ]
Feng, Lei [3 ]
Kadara, Humam [2 ]
Kim, Hyun-Jung [2 ]
Lee, J. Jack [3 ]
Mehran, Reza [4 ]
Hong, Waun Ki [2 ]
Lotan, Reuben [2 ]
Wistuba, Ignacio I. [1 ,2 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Unit 85, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA
关键词
NF-KAPPA-B; BRONCHIAL EPITHELIAL-CELLS; GENE-EXPRESSION; INNATE IMMUNITY; MICROARRAY DATA; TUMOR-GROWTH; CANCER; TOLL; ADENOCARCINOMA; IDENTIFICATION;
D O I
10.1158/1078-0432.CCR-09-0650
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-kappa B and IL-1 alpha 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-1 alpha 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-kappa B 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); 34-44. (C) 2010 AACR.
引用
收藏
页码:34 / 44
页数:11
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