NLRP6 is correlated with the progression and therapeutic outcome of hepatocellular carcinoma and inhibits the function of CD14+ cells

Objective: Inflammasomes promote carcinogenesis throughan extrinsic pathway and maintain the malignant cancermicroenvironment through an intrinsic pathway. Moreover,inflammasomes exert anticancer effects by pyroptosis andimmune regulatory functions. Until now, there have been fewstudies about how inflammasomes contribute to hepatocellularcarcinoma (HCC) development. The aims of the present studywere to investigate the expression profiles of inflammasomecomponents and the correlation of inflammasome componentswith the progress and treatment outcomes in HCC. Methods: The expression levels of various inflammasomecomponents were detected by RT-qPCR in peripheral bloodmononuclear cells (PBMCs) from HCC, liver cirrhosis (LC)and chronic hepatitis patients, and healthy controls (HC). Themost obviously changed genes were selected. The associationbetween their expression profiles and lymphocyte subsets, HCCprogression (according BCLC), and prognosis was furtheranalyzed. Their functions were investigated in vitro. Results: The nod-like receptor family, pyrin domain containing6 (NLRP6), nod-like receptor family, CARD domain containing4 (NLRC4), and NLRP7 had significantly higher expressionin PBMCs from HCC patients than either LC or HC groups(P < 0.05). We analyzed the correlation between the expressionof these inflammasome components with HCC progression.We observed that only the expression of NLRP6 was significantly correlated with the progression of HCC (P < 0.05).Moreover, NLPR6 expression in PBMCs from HCC patientswho relapsed within a year after resection was significantlydifferent from that of HCC patients without relapse (P < 0.05).Flow cytometric analysis showed that NLRP6 was highlyexpressedin a CD14+ subset of PBMCs and the frequency ofCD14+NLR6+ in the HCC group was higher than that in HC.In vitro assays showed that overexpression of NLRP6 in theTHP-1 cell line inhibited its proliferation and polarization. Conclusions: High expression of NLRP6 inhibited theproliferation and polarization of the THP-1 cell line, and highexpression of NLRP6 in PBMCs was significantly correlatedwith HCC progression and poor prognosis. NLRP6 couldbe a prognostic marker and novel therapeutic target forhepatocellular carcinoma. DOI: 10.20892/j.issn.2095-3941.2018.S046