Dataset Information

NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma.

ABSTRACT: Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients. Data from 360 HCC patients in The Cancer Genome Atlas database and 231 patients in the Gene Expression Omnibus database were analyzed. Kaplan-Meier analysis and a Cox regression model were used to determine median survival time (MST) and overall and recurrence-free survival by calculating the hazard ratio (HR) and 95% confidence interval (CI). High NOD2 and low NLRX1 expression in tumor tissue was associated with short MST (P = 0.012 and 0.014, respectively). A joint-effects analysis of NOD2 and NLRX1 combined revealed that groups III and IV had reduced risk of death from HCC as compared to group I (adjusted P = 0.001, adjusted HR = 0.31, 95% CI = 0.16-0.61 and adjusted P = 0.043, adjusted HR = 0.63, 95%CI = 0.41-0.99, respectively). NOD2 and NLRX1 expression levels are potential prognostic markers in HCC following hepatectomy.

SUBMITTER: Wang X

PROVIDER: S-EPMC5673949 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma.

Wang Xiangkun X Yang Chengkun C Liao Xiwen X Han Chuangye C Yu Tingdong T Huang Ketuan K Yu Long L Qin Wei W Zhu Guangzhi G Su Hao H Liu Xiaoguang X Ye Xinping X Chen Bin B Peng Minhao M Peng Tao T

Cancer medicine 20170929 11

Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients. Data from 360 HCC patients in The Cancer Genome Atlas database and 231 patients in the Gene Expression Omnibus database were analyzed. Kaplan-Meier analysis an ...[more]

PMID: 28960882

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Project description:BackgroundThe copper metabolism MURR1 domain (COMMD) protein family involved in tumor development and progression in several types of human cancer, but little is known about the function of COMMD proteins in hepatocellular carcinoma (HCC).MethodsThe ONCOMINE and the UALCAN databases were used to evaluate the expression of COMMD1-10 in HCC and the association of this family with individual cancer stage and tumor grade. Kaplan-Meier (K-M) Plotter and Cox analysis hint the prognostic value of COMMDs. A network comprising 50 most similar genes and COMMD1-10 was constructed with the STRING database. Gene set enrichment analysis (GSEA) was performed using LinkedOmics database. The correlations between COMMD expression and the presence of immune infiltrating cells were also analyzed by the tumor immune estimation resource (TIMER) database. GSE14520 dataset and 80 HCC patients were used to validated the expression and survival value of COMMD3. Human HCC cell lines were also used for validating the function of COMMD3.ResultsThe expression of all COMMD family members showed higher expression in HCC tissues than that in normal tissues, and is associated with clinical cancer stage and pathological tumor grade. In HCC patients, the transcriptional levels of COMMD1/4 are positively correlated with overall survival (OS), while those of COMMD2/3/7/8/9 are negatively correlated with OS. Multivariate analysis indicated that a high level of COMMD3 mRNA is an independent prognostic factor for shorter OS in HCC patients. However, the subset of patients with grade 3 HCC, K-M survival curves revealed that high COMMD3/5/7/8/9 expression and low COMMD4/10 expression were associated with shorter OS. In addition, the expression of COMMD2/3/10 was associated with tumor-induced immune response activation and immune infiltration in HCC. The expression of COMMD3 from GSE14520 dataset and 80 patients are both higher in tumor than that in normal tissue, and a higher level of COMMD3 mRNA is associated with shorter OS. Knockdown of COMMD3 inhibits human HCC cell lines proliferation in vitro.ConclusionsOur study indicates that COMMD3 is an independent prognostic biomarker for the survival of HCC patients. COMMD3 supports the proliferation of HCC cells and contributes to the poor OS in HCC patients.

Project description:Hepatocellular carcinoma (HCC) is a global health challenge with an increasing incidence worldwide. Cancer-associated fibroblasts (CAFs) function critically in HCC initiation and development. However, the prognostic significance of CAF-related gene signatures in HCC remains unknown. Therefore, the specific functions of CAF-related genes in HCC were investigated to help develop potential therapeutic strategies. In this study, CAF-related genes were screened from three CAF-related gene sets. HCC data from the Gene Expression Omnibus (GEO) database was applied to verify the screened CAF-related genes. Cluster analysis was used to identify clusters based on the expression pattern of CAF-related genes and two identified clusters were found to have a significant difference in overall survival (OS) and progression free intervals (PFI). The prognosis of HCC patients was predicted using the prognostic risk score model developed based on HCC data from The Cancer Genome Atlas (TCGA) databases. High-risk group patients had a worse OS than those in low-risk group in TCGA. These results were validated in International Cancer Genome Consortium (ICGC) database. Moreover, combining the clinicopathological characteristics related to prognosis with the model, a nomogram was built for a more accurate prediction of OS of HCC patients. In addition, analyses of immune infiltration characteristics of tumor microenvironment (TME), chemosensitivity, and immunotherapy response were conducted to further evaluate the prognostic value of CAF-related genes. Patients with low-risk scores were found to have higher chemosensitivity to cisplatin, doxorubicin, and sorafenib. Individuals with high-risk scores were found with a higher expression of most immune checkpoints which indicated patients with high-risk scores may benefit more from treatment with immune checkpoint inhibitors. Furthermore, a correlation between immune infiltration characteristics of TME and patients with different risk levels was found. These findings provide a possibility for the further development of personalized treatments in HCC.

Dataset Information

NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma.

Publications

NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma.

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