Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components

// Rongrong Liu 1,2,* , Agnieszka D. Truax 2,* , Liang Chen 2 , Peizhen Hu 3 , Zengshan Li 3 , Jun Chen 4 , Chaojun Song 1 , Lihua Chen 1 and Jenny Pan-Yun Ting 2,5 1 Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi’an, China 2 The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 3 Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, China 4 Department of Encephalopathy, Traditional Chinese Medicine Hospital of Shan Xi Province, Xi’an, China 5 Departments of Genetics, Microbiology-Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA * These authors have contributed equally to the work Correspondence to: Jenny Pan-Yun Ting, email: // Lihua Chen, email: // Keywords : NLRs, AIM2, FFPE, colorectal cancer, inflammasome Received : August 02, 2015 Accepted : August 20, 2015 Published : September 10, 2015 Abstract NLRs (nucleotide-binding domain leucine-rich repeat proteins or NOD-like receptors) are regulators of inflammation and immunity. A subgroup of NLRs and the innate immune receptor, AIM2 (absent-in-melanoma 2), can induce the assembly of a large caspase-1 activating complex called the inflammasome. Other NLRs regulate key signaling pathways such as NF-kB and MAPK. Since inflammation is a central component of colorectal cancer (CRC), this work was undertaken to analyze NLR and AIM2 expression in human CRC by combining bioinformatics analysis and experimental verification using clinical tissue samples. Additional experiments analyzed the association of (i) gene expression and cancer staging, and (ii) gene expression among inflammasome components. Ten public CRC datasets from the Oncomine ®  Platform were analyzed. Genes analyzed include NLRP1, NLRP3, NLRP6, NLRP12, NLRC3, NLRC4, NLRC5, NOD1, NOD2 and AIM2. Additionally, forty case-matched cancer samples and adjacent healthy control tissues isolated from a cohort of Chinese CRC patients were profiled. Three patterns of gene expression in CRC are shown. The expression of NLRC3, a checkpoint of inflammation, and the inflammasome components NLRP1, NLRP3, NLRC4 and AIM2 were reduced in CRC. NOD1 and NOD2 expression was increased in CRC, while NLRC5, NLRP6 and NLRP12 showed little difference compared to controls. Reduced expression of NLRC3 in CRC was verified in all available databases analyzed and confirmed with our patient cohort. Furthermore, the extent of NLRC3 and AIM2 gene reduction was correlated with cancer progression. This report reveals the potential value of NLR and AIM2 genes as biomarkers of CRC and cancer progression.