Dataset Information

Mining Database for the Expression and Clinical Significance of NF-?B Family in Hepatocellular Carcinoma.

ABSTRACT: Background:Hepatocellular carcinoma (HCC) is one of the deadliest diseases affecting humans. Its incidence has been increasing over the last decade. It is characterized by poor prognosis as well as lack of therapeutic regimens for patients in the advanced stages. It is therefore important to develop effective biomarkers for diagnosis, prognosis, and immunotherapy of HCC. Research suggests that the NF-?B family plays vital roles in immune response, inflammation, tumorigenesis, and the progress of malignancy in various cancers. However, its role in HCC remains unidentified. Methodology. The expression and clinical significance of the NF-?B family in HCC were analyzed using several bioinformatics tools including UALCAN, The Human Protein Atlas, GEPIA, GSCALite, David, GeneMANIA, and TIMER. Results:The mRNA expression levels of RelA, RelB, NF-?B1, and NF-?B2 were significantly elevated in HCC. The mRNA levels of RelB and NF-?B2 were significantly upregulated in HCC tissues compared to normal liver tissues in subgroup analyses based on patient's race, gender, age, weight, tumor grade, cancer stage, and nodal metastasis status. Moreover, HCC patients with elevated levels of RelB and NF-?B2 had a worse overall survival and disease-free survival. Methylation downregulated the expressions of RelA, RelB, and NF-?B1 in HCC. NF-?B family was also significantly involved in various hallmark cancer-related pathways such as the apoptosis, EMT, RTK, and cell cycle pathways. Similarly, the expression of RelB and NF-?B2 was positively correlated with the abundance of immune cells and the expression of immune biomarkers. Several kinase and miRNA targets of RelB and NF-?B2 were also identified. Conclusion:RelB and NF-?B2 are potential biomarkers for the diagnosis, prognosis, and immunotherapy of HCC.

SUBMITTER: Chen X

PROVIDER: S-EPMC7448221 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mining Database for the Expression and Clinical Significance of NF-<i>κ</i>B Family in Hepatocellular Carcinoma.

Chen Xu X Zhou Yufan Y Li Zhecheng Z Wang Zhiming Z

Journal of oncology 20200817

<h4>Background</h4>Hepatocellular carcinoma (HCC) is one of the deadliest diseases affecting humans. Its incidence has been increasing over the last decade. It is characterized by poor prognosis as well as lack of therapeutic regimens for patients in the advanced stages. It is therefore important to develop effective biomarkers for diagnosis, prognosis, and immunotherapy of HCC. Research suggests that the NF-<i>κ</i>B family plays vital roles in immune response, inflammation, tumorigenesis, and ...[more]

PMID: 32879628

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Project description:NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.

Project description:PurposeGamma-glutamyl transpeptidase (GGT) family genes play crucial roles in the formation and progression of several solid tumors. However, the expression patterns and the prognostic significance of GGT members in hepatocellular carcinoma (HCC) remain unknown. This study was designed to determine the expression profiles of GGT family members in HCC and validate the prognostic value of serum GGT protein in patients with HCC.MethodWe comprehensively searched public resources based on the LIHC dataset to determine the expression patterns, prognostic significance, DNA methylation status, immune infiltration, and biological pathways of GGT family genes in HCC. Subsequently, we validated the prognostic value of serum GGT protein in 85 patients with early-stage HCC subjected to curative hepatectomy from the Renmin Hospital of Wuhan University.ResultsExcept for GGT1, other GGT family members (GGT5, GGT6, and GGT7) were found to be differentially expressed in primary HCC samples (N = 371) and normal control tissues (N = 50). Furthermore, a positive relationship was not only observed between GGT1 and GGT5 (Spearman coefficient: 0.24, P = 5.143 × 10-6) but also between GGT5 and GGT6 (Spearman coefficient: 0.38, P = 1.24 × 10-13). The expression of GGT1, GGT5, and GGT7 was correlated with overall survival (OS), and GGT7 was associated with disease-free survival (DFS) in patients with HCC. Negative associations between DNA methylation and expression of mRNA were observed for GGT1 (Spearman coefficient: -0.38, P = 6.24e-14), GGT6 (Spearman coefficient: -0.29, P = 1.23e-8), and GGT7 (Spearman coefficient: -0.34, P=6.7e-11). GGT family genes were well correlated with the infiltration levels of immune cells in HCC, especially CD4+ T cells, macrophages, and dendritic cells. Finally, when validated with clinical data from the Renmin cohort, a high expression of serum GGT protein was identified as a strong prognostic element of unfavorable OS (HR = 3.114, P = 0.025), but not of DFS (HR = 1.198, P = 0.05) in patients with HCC subjected to curative hepatectomy.ConclusionTo our knowledge, this is the first comprehensive analysis of the expression patterns and clinical value of GGT family genes in patients with HCC. Our study laid the foundation for the clinical application of the GGT protein in the survival assessment of patients with HCC.

Dataset Information

Mining Database for the Expression and Clinical Significance of NF-?B Family in Hepatocellular Carcinoma.

Publications

Mining Database for the Expression and Clinical Significance of NF-<i>κ</i>B Family in Hepatocellular Carcinoma.

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