Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Objective: The aim of this study was to investigate the role of matrix metallopeptidase 12 (MMP-12) in the development of hepatocellular carcinoma (HCC). Materials and Methods: A total of 343 HCC patients were retrospectively analyzed. MMP-12 expression was detected by immunohistochemical staining and the correlation between MMP-12 expression and clinical features was analyzed. Serum interleukin-6 (IL-6) and IL-10 levels were detected by an enzyme-linked immunosorbent assay (ELISA). Survival analysis was performed using the Kaplan-Meier method and PD-L1 expression in T cells was detected by flow cytometry. Results: MMP-12 expression in HCC tissues showed no correlation with age, gender, viral infection, cirrhosis, Child-Pugh score, alpha-fetoprotein levels, or Barcelona-Clinic Liver Cancer stage. However, higher levels of MMP-12 expression were correlated with increased tumor size, poorer tumor cell differentiation, higher TNM stage, and poorer prognosis. Moreover, MMP-12 expression was positively correlated with PD-L1 expression. Further analysis indicated that the regulation of PD-L1 expression by MMP-12 may occur through the IL-6-signaling pathway. Conclusions: Higher levels of MMP-12 expression indicated a poorer prognosis. PD-L1 expression was positively correlated with MMP-12 expression, indicating that MMP-12 may promote the development of HCC through the up-regulation of PD-L1.
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PMID:Role of Matrix Metallopeptidase 12 in the Development of Hepatocellular Carcinoma. 3130 19

NADPH oxidase (NOX) is a key source of reactive oxygen species (ROS). This study aimed to verify NOX2 and NOX4 expression levels in hepatocellular carcinoma (HCC). A total of 134 matched pairs of HCC cells and non-tumour hepatocytes from 134 patients were examined by immunohistochemical staining, and the association of NOX2 and NOX4 expression with clinicopathological parameters was analysed. Western blotting in four HCC cell lines and reverse transcription digital droplet polymerase chain reaction (RT-ddPCR) in 20 pairs of HCC and non-tumour tissue samples were also performed to detect NOX4. Cytoplasmic NOX2 and nuclear NOX4 expression levels were shown by immunohistochemistry to be higher in HCC cells than in non-tumour hepatocytes (p<0.001 each). The western blotting results for NOX4 in four HCC cell lines were consistent with the immunohistochemical results. Increased cytoplasmic expression of NOX2 and NOX4 in HCC cells was significantly correlated with liver cirrhosis (p<0.001 and p<0.031, respectively). However, decreased cytoplasmic expression of NOX2 and NOX4 was significantly correlated with advanced pathological TNM stage (p<0.029 and p<0.007, respectively). Multivariate analysis with clinicopathological parameters showed that high nuclear and low cytoplasmic NOX4 expression levels are correlated with short overall survival (p=0 .021). Our findings imply that cytoplasmic NOX2 and nuclear NOX4 expression is upregulated during HCC development. In particular, NOX4 translocation into the nucleus may affect the development and progression of HCC. NOX2 and NOX4 could be diagnostic markers and have therapeutic implications in HCC.
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PMID:High nuclear NADPH oxidase 4 expression levels are correlated with cancer development and poor prognosis in hepatocellular carcinoma. 3144 22

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a member of the cell cycle-dependent protein kinase subunit family, which is implicated as an oncogene in various malignancies. However, the clinical significance, oncogenic functions, and related mechanisms of CKS2 in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, expression features and prognostic value of CKS2 were evaluated in the bioinformatic databases and HCC tissues. The effects of CKS2 on the malignant phenotypes of HCC cells were explored in vitro. According to the analyses of three bioinformatic databases, mRNA levels of CKS2 were elevated in HCC tissues compared with the normal tissues. Immunohistochemical assays found that high CKS2 expression was closely associated with liver cirrhosis (P = 0.019), poor differentiation (P = 0.02), portal vein invasion (P < 0.001), TNM stage (P = 0.019), tumor metastasis (P = 0.008), and recurrence (P = 0.003). The multivariate regression analyses suggested that CKS2 was an independent prognostic factor for overall survival (HR = 2.088, P = 0.014) and disease-free survival (HR = 2.511, P = 0.002) of HCC patients. Moreover, the bioinformatic analyses indicated that CKS2 might be associated with the malignant phenotypes in HCC progression. In addition, in vitro assays showed that CKS2 expression was higher in HCC cell lines than in normal liver cells. Knockdown of CKS2 remarkably repressed the proliferation, colony formation (P = 0.0003), chemoresistance, migration (P = 0.0047), and invasion (P = 0.0012) of HCC cells. Taken together, overexpression of CKS2 was significantly correlated with poor prognosis of HCC patients and the malignant phenotypes of HCC cells, suggesting that it was a novel prognostic biomarker and potential target of HCC.
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PMID:Cyclin-Dependent Kinase Regulatory Subunit 2 Indicated Poor Prognosis and Facilitated Aggressive Phenotype of Hepatocellular Carcinoma. 3178 10

Fibrinogen C domain-containing 1 (FIBCD1) is an acetyl-recognition receptor that affects the occurrence and development of certain tumors. However, the prognostic significance of FIBCD1 in hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore FIBCD1 expression in HCC and to determine the prognostic value of FIBCD1 in patients with HCC. A total of 1,058 liver tissue samples with detailed and complete clinical information were collected, including 495 HCC samples. Tissue microarray immunohistochemistry analysis was used to evaluate FIBCD1 protein expression in the collected tissues. The Kaplan-Meier plotter online tool was used to investigate the association between FIBCD1 expression and prognosis of patients with HCC. Oncomine and the Gene Expression Profiling Interactive Analysis database were used for bioinformatics analysis of FIBCD1. Results showed that FIBCD1 expression was higher in HCC and was associated with tumor diameter (P=0.002), tumor number (P=0.001), tumor node metastasis stage (P<0.001), primary tumor (T; P<0.001), lymph node metastases (N; P=0.002), distant metastases (M; P=0.023), differentiation degree (P=0.003), vascular invasion (P<0.001) and liver cirrhosis (P=0.011). Patients with HCC and high FIBCD1 expression had worse overall survival than those with low FIBCD1 expression. High FIBCD1 expression (P<0.001), TNM stage (P=0.003), T (P<0.001), N (P=0.014), and vascular invasion (P<0.001) were independent prognostic factors in HCC. Hence, FIBCD1 may be a novel biomarker for prognosis evaluation of HCC.
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PMID:FIBCD1 overexpression predicts poor prognosis in patients with hepatocellular carcinoma. 3189 96

Human RING-finger protein 40 (RNF40) is reported as an E3 ligase of H2B ubiquitination. RNF40 needs to couple with its homolog RNF20 to format a complex to regulate DNA double strand break (DSB) response and chromatin stability. Deficient expression of RNF40 might cause incorrect DNA repair and contribute to genomic instability, leading to an abnormal transcriptional program. Incorrect DSB repair and aberrant gene transcription play important roles in tumorigenesis. The role in primary hepatocellular carcinoma (HCC), however, remains unclear. In this study, we selected 103 cases of HCC for immunohistochemistry to explore the role of RNF40 in HCC. The relationship between RNF40 expression and clinicopathological features of HCC was evaluated. RNF40 was mainly localized in the nucleus, where the percentage of low and high staining of RNF40 in tumor tissues was 50.4% (53/103) and 49.6% (50/103), respectively. By contrast, in para-normal tissues the percentage was 92.2% (95/103) and 7.8% (8/103) respectively. Expression of RNF40 in tumor tissues was significantly higher than that in para-normal tissues (P>0.01). Expression of RNF40 had significant association with AFP and TNM tumor stage (both P>0.01). However, age, gender, Hepatitis B Virus infection, liver cirrhosis, tumor size, tumor number, differential stage, and tumor thrombosis were not associated with RNF40 expression. Meanwhile, HCC patients with high expression of RNF40 had lower 5 year overall survival rates and disease-free survival rates (P>0.05). RNF40 is, potentially, an independent prognostic factor for survival in HCC.
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PMID:High RNF40 expression indicates poor prognosis of hepatocellular carcinoma. 3193 14

The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12-1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85-1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81-2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20-3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16-1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54-0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55-0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06-10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.
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PMID:Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis. 3225 89

We reviewed all studies assessing the health-related quality of life (HRQoL) in patients with hepatocellular carcinoma (HCC) between 2009 and 2018 (n = 45). Most studies assessed HRQoL as an outcome, and evaluated or compared the HRQoL of HCC patients depending on the type of treatment or stage of disease. HCC patients had a worse HRQoL than the general population, including in those with early-stage HCC. Patients commonly experienced pain, fatigue, sleep disturbance, distress, and lack of appetite, and these symptoms remained problematic even a few years after treatment. TNM classification of malignant tumors stage, tumor stage, presence of cirrhosis, being Asian, being female, living alone, or being unemployed were associated with a poor HRQoL. While recent studies have included a more diverse patient population, various topics, and different study designs, there were limited studies on supportive interventions. Given the increase in HCC cases and HCC survivors, addressing the HRQoL of HCC patients requires more attention.
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PMID:Systematic Review of Studies Assessing the Health-Related Quality of Life of Hepatocellular Carcinoma Patients from 2009 to 2018. 3241 Apr 3

HBV-associated hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and non-invasive early detection of HBV-associated HCC requires to be improved. To determine the alteration and clinical relevance of necroptosis and its key regulator receptor-interacting protein kinase 3 (RIPK3) in HBV-associated HCC, we detected the mRNA level of RIPK3 in peripheral blood mononuclear cells (PBMCs) and analyzed its correlation with clinical parameters. Here, we demonstrate that the expression of RIPK3 is elevated in patients with HBV-associated HCC compared to patients with chronic hepatitis B (CHB) and patients with HBV-related liver cirrhosis (LC). The mRNA level of RIPK3 is positively correlated with the severity of clinical manifestations and TNM stages. Moreover, the serum levels of RIPK3-asssocited cytokines are altered in consistent with the change of RIPK3 expression. The diagnostic accuracy of RIPK3 mRNA level is comparable to AFP test in discriminating HBV-associated HCC from LC and is better than AFP test in discriminating HBV-associated HCC from CHB. The combination of RIPK3 mRNA level and AFP test significantly improves the diagnosis of HBV-associated HCC. These data suggest that RIPK3 mRNA level is a biomarker in the onset and progression of HBV-associated HCC and may provide novel diagnostic strategies combined with the AFP test.
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PMID:RIPK3 mRNA level acts as a diagnostic biomarker in hepatitis B virus-associated hepatocellular carcinoma. 3285 63

To investigate the expression level and clinical significance of fucosidase (AFU), glutamyltranspeptidase (GGT), and thymidine kinase 1 (TK1) in the serum of patients with primary liver cancer (PHC). A total of 135 PHC patients in Baoji Central Hospital from September 2014 to February 2018 were selected as a research group (RG), while 127 healthy subjects were collected as a control group (CG). Enzyme-linked immunosorbent assay (ELISA) was used to detect the AFU, GGT, and TK1 concentrations in serum of the two groups, and the diagnostic value of combined detection of the three for PHC was analyzed. AFU, GGT, and TK1 concentrations in serum of the RG were dramatically higher than those of the CG (P&lt; 0.050). ROC curve analysis showed that the sensitivity of AFU, GGT, and TK1 in the single diagnosis of PHC was 88.00, 94.00, and 66.00% respectively, and the specificity was 68.00, 54.00, and 66.00% respectively. The sensitivity and specificity of the combined diagnosis of PHC were 76.00 and 90.00%, respectively. AFU, GGT, and TK1 concentrations were different in the presence or absence of liver cirrhosis, TNM stage, and tissue type (P&lt; 0.050). AFU, GGT, and TK1 concentrations in PHC patients were dramatically higher than those in healthy people. Combined detection of the three has good diagnostic value for PHC.
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PMID:Serum AFU, GGT and TK1 levels in PHC patients and their correlation with clinicopathology and diagnostic value. 3304 Aug 23


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