Abstract 3423: Expression level of inflammasomes compornents NLRP3, NLRC4, and CASP1 in background non tumorous tissue were associated with worse prognosis for curatively resected hepatocellular carcinoma

Abstract

Abstract Background and Objectives: When assessing hepatocellular carcinoma (HCC), it is quite important to examine prognostic factors in the background non tumorous liver tissue as well as HCC tissue itself. Inflammation has been thought to have some influence to malignancy of neoplasms and carcinogenesis. We focused on inflammasomes; multiprotein complex evoking key cascades of inflammation. Components of inflammasomes are investigated in mRNA level to identify molecular prognostic predictors for curatively resected HCC. Methods: Candidate genes that code pattern recognition receptors ; NLRP3, NLRC4, and AIM2 and caspase1 (CASP1) that mature IL-1β, IL-18 were investigated via real-time quantitative reverse transcription polymerase chain reaction in 158 consecutive curatively resected HCC cases at our department. We investigated each gene expression in both HCC tumor tissue (T) and background corresponding non tumorous tissue (CN) and super normal tissue (SN) taken from resected specimens of metastatic hepatic tumor was also assessed in this study. Statistical analyses were performed with Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional hazards models were used to determine the independent risk factors associated with the RFS and OS. Results: The expression level of NLRP3, NLRC4, and AIM2 (expression score/GAPDH×1000) were significantly higher in CN (NLRP3 median: 0.29 [range: 0.037-10.59], NLRC4 0.38[0.010-9.85] , AIM2 1.00 [0.016-43.62], n = 158 ) than in T (NLRP3 0.064 [0.0027-41.67] P<0.0001, NLRC4 0.14 [0.0044-6.14] P<0.0001, AIM2 0.24 [0.0017-18.23] P<0.0001, n = 158) and SN (NLRP3 0.10 [0.029-0.74] P = 0.0026, NLRC4 0.090[0.032-0.16] P<0.0001, AIM2 0.15 [0.053-1.30] P = 0.0003, n = 11). CASP1 in CN (3.26 [0.34-32.95] n = 158) was significantly higher than that in T (1.43 [0.13-40.98] P<0.0001, n = 158). 158 HCC cases were subsequently divided into two groups based on NLRP3, NLRC4, and CASP1 expression in T and CN in each case. NLRP3 in CN ≥ median, NLRC4 in CN ≥ median, and CASP1 in CN ≥ median cases demonstrated significant correlation with worse overall survival respectively (NLRP3 P = 0.0074, NLRC4 P = 0.0121, CASP1 P = 0.0160). Furthermore, multivariate analysis identified NLRP3 expression in CN ≥ median as an independent prognostic factor in overall survival (P = 0.0011). Conclusions: Our findings suggested that NLRP3, NLRC4, and CASP1 expression in CN were significantly correlated with curatively resected HCC prognosis. Inflammation in background non tumorous tissue might be related with HCC malignancy and those were putative biomarker for curatively resected HCC. Citation Format: Fuminori Sonohara, Shuji Nomoto, Yoshikuni Inokawa, Mitsuro Kanda, Suguru Yamada, Tsutomu Fujii, Masahiko Koike, Hiroyuki Sugimoto, Michitaka Fujiwara, Yasuhiro Kodera. Expression level of inflammasomes compornents NLRP3, NLRC4, and CASP1 in background non tumorous tissue were associated with worse prognosis for curatively resected hepatocellular carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3423. doi:10.1158/1538-7445.AM2015-3423