Abstract 1926: Nod-like receptors family member- NLRC5 as a useful prognostic marker in renal cell carcinomas.

Abstract

Abstract Based on our previous methylated-CpG island recovery assay (MIRA) combined with DNA microarray technique studies, several hypermethylated genes have been proven in renal cell carcinoma (RCC), in which NLRC5 was one of the interested genes. To our knowledge, this is the first study of NLRC5 in RCCs. NLRC5 was a member of the Nod-like receptors family proteins that contains C-terminal leucine-rich repeat (LRR) domain, nucleotide-binding NACHT domain and the CARD domain. It is commonly highly expressed in many immune related tissues, such as bone marrow, lymph node, spleen, thymus; besides, it also presented in normal tissues, such as kidney, liver and prostate. The function of NLRC5 has been widely proven in immunoactivities, it was known may negative regulated NF-κB and type I interferon signaling pathways, however, seldom to be studied in tumorigenesis neoplastic progression. Therefore, it led our attention to the expression of NLRC5 might regulate NF-κB activity, then further promoting the pathogenesis and metastatic behavior of RCC. Herein, we hypothesized that via demethylated NLRC5 might indirect inactivation of NF-κB then result in reducing the cancer cell proliferation. In this study we aimed to investigate the status of methylation and mRNA expression of NLRC5 in RCC. We performed reverse transcription PCR on six RCC cell lines, which included chromophobe type RCC98, sacomatoid type RCC52, clear cell type RCC100, and papillary type HH050 RCC cell lines were derived from Chang Gung Memorial Hospital, Taiwan; 786-O and HEK-293 were commercial available, in which 5-aza-2’deoxycytidine was treated on randomly selected cell lines RCC98, 786-O and HH050 to demethylate the DNA. Real-time PCR were than performed on 75 pairs of clinical RCCs samples (tumor tissue v.s normal tissue), the results were divided into two groups, high expression (T/N≥ 1.5) and low expression (T/N <1.5), the Kaplan-Meier procedure then calculated the survival probability estimate for each of the time periods. The results showed that variant gene expression of the NLRC5 could be observed from all RCC cell lines. Generally, the tumors were considered as poor prognostic types (e.g. RCC100 and RCC52) presented lower level of NLRC5 expression, except 786-O cell line. Survival analysis of the NLRC5 expression of 75 pairs RCC patients, high expression of NLRC5 associated with better disease-free survival and overall survival, p = 0.015 and 0.04, respectively; however, it was not correlated to pT stage and grade. Interestingly, after treated with the demethylated drug on tested cell lines, the expressed level of NLRC5 was restored in all tested cells. We concluded that high expression of NLRC5 was correlated with better patient survival, and it might be used as a prognostic marker to predict patient outcomes in RCC. Besides, the epigenetic demethylation of NLRC5 was suggested it could be a potential way for treatment with RCC. Citation Format: Ying-Tzu Chen, Wen-Hui Weng, See-Tong Pang. Nod-like receptors family member- NLRC5 as a useful prognostic marker in renal cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1926. doi:10.1158/1538-7445.AM2013-1926