NLRC3 High Expression Represents a Novel Predictor for Positive Overall Survival Correlated With CCL5 and CXCL9 in HCC Patients

Chengpan Wang; Jieyi Shi; Jietian Xu; Qiaoyu Fu; Youpeng Ding; Jessie Yang; Binbin Liu; Qiang Gao; Jie Qin; Chunmin Liang

doi:10.3389/fonc.2022.815326

NLRC3 High Expression Represents a Novel Predictor for Positive Overall Survival Correlated With CCL5 and CXCL9 in HCC Patients

Front Oncol. 2022 Jan 25:12:815326. doi: 10.3389/fonc.2022.815326. eCollection 2022.

Authors

Affiliations

¹ Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China.
² Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.

Abstract

NLRC3 (NLR family caspase recruitment domain containing 3) has been reported as a factor of inhibiting inflammatory responses. It's role in HCC (hepatocellular carcinoma) is still unknown. In this study we firstly used the GEO (Gene Expression Omnibus) database and mIHC (multiple immunohistochemical analysis) with TMAs (tumor tissue microarrays) of HCC patients to evaluate NLRC3 levels. The tumor-bearing mouse models were also established with NLRC3 over-expressing and knock-down Hepal-6 cells to assess its effect. The data showed high NLRC3 expression was related with favorable overall survival (P=0.0386) and disease-free survival (P=0.0458). In addition, NLRC3 expression showed a positive correlation between CD8⁺ T cells infiltration. In vivo, NLRC3-overexpressing Hepal-6 tumors showed increased CD8⁺ T cell infiltration. NLRC3-knockdown Hepa1-6 tumors displayed decreased CD8⁺ T cell infiltration. At the same time, we also found the positive correlations between NLRC3 and CCL5 (C-C motif chemokine ligand 5, P<0.0001, R² = 0.2372) as well as CXCL9 (C-X-C motif chemokine ligand 9, P<0.0001, R² = 0.2338) expressions. So NLRC3 high expression represents a novel predictor for positive survival outcomes in HCC patients, and NLRC3 is involved in CD8⁺ T cell infiltration, which is correlated with increased CCL5 and CXCL9 in TME (tumor microenvironment). This study implies that boosting NLRC3 is a promising treatment to enhance survival in HCC patients.

Keywords: CCL5; CD8+ T cell; CXCL9; NLRC3; hepatocellular carcinoma; overal survival.