scholarly journals Downregulation of LHPP Expression Associated with AFP Acts as a Good Prognostic Factor in Human Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xu Chao ◽  
Wei Zhang ◽  
Jieqiong Wu ◽  
Xuesong Feng ◽  
Hailong Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Rank Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gamma Glutamyl Transferase ◽  
Clinical Parameters ◽  
Inorganic Pyrophosphate ◽  
Normal Tissues ◽  
Glutamyl Transferase ◽  
Hcc Cells

Background. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma (HCC), but the correlation between the expression of LHPP and the clinical parameters of oncogenic progression is still not well defined. This study is to reveal the correlation between the expression of LHPP in HCC and their clinical parameters. Methods. Immunohistochemical analysis was used to assess the correlation between the expression of LHPP and the clinical parameters of HCC. Expressions of LHPP in HCC tissues and cultured HCC cells were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). LHPP, gamma-glutamyl transferase (GGT), and α-fetoprotein (AFP) expression levels in blood or HCC tissues were detected by enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation coefficient was used to evaluate the correlation of the expression of LHPP and the clinical index of HCC. Correlation of survival and expression of LHPP were analyzed using the Kaplan-Meier method and the log-rank test. Results. Expressions of LHPP in HCC tissues were significantly downregulated than their paired adjacent normal tissues. A significant positive correlation was found between the cytoplasm and nuclear expression of LHPP in both HCC and their paired adjacent normal tissues. The expression of LHPP negatively correlated with the levels of GGT in the cytoplasm of adjacent tissues and with the AFP level in the nucleus of HCC cells. Relative levels of LHPP in HCC tissues were markedly lower than those of the paired adjacent normal tissues. Relative levels of LHPP in LO-2 cells were higher than those of HepG2, BEL-7404, and SMMC-7721 cell lines. The overall survival and DSF survival of patients with the high expression of LHPP were much higher than those with the low expression of LHPP in paired adjacent normal tissue. Conclusions. LHPP is associated with the AFP level and acts as a good prognostic factor in HCC.

Anticancer Effects of Tacrolimus on Induced Hepatocellular Carcinoma in Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Shireen Sami Mahmoud ◽  
Samia Hussein ◽  
Hayam Rashed ◽  
Eman M. A. Abdelghany ◽  
Alaa I. Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cyclin D1 ◽  
Liver Enzymes ◽  
Combined Treatment ◽  
Treated Group ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gamma Glutamyl Transferase ◽  
Anticancer Effects ◽  
Glutamyl Transferase

Background: Tacrolimus is a calcineurin inhibitor widely used for immunological disorders. However, there is a significant controversy regarding its effect on the liver. The present study was conducted to evaluate the anticancer effects of tacrolimus on an induced murine hepatocellular carcinoma (HCC) model and its possible hepatotoxicity at standard therapeutic doses. Methods: Fifty-four male mice were divided into five groups: a control healthy group, control HCC group, tacrolimus-treated group, doxorubicin (DOXO)-treated group, and combined tacrolimus- and DOXO-treated group. The activity of liver enzymes, including alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, alanine transaminase, and aspartate transaminase, was determined. Serum vascular endothelial growth factor (VEGF) was measured using an enzyme-linked immunosorbent assay. A quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the expression of proliferating cell nuclear antigen (PCNA), Bax, and p53 mRNA. Immunohistochemical staining for cyclin D1 and VEGF was performed. Results: Mice that received combined treatment with tacrolimus and DOXO exhibited the best improvement in all parameters when compared with the groups that received DOXO or tacrolimus alone (p < 0.001). Conclusion: The combination of DOXO and tacrolimus was more effective in the management of HCC compared with either agent alone. This improvement was detected by the reduction of liver enzymes and the improvement of the histopathological picture. The involved mechanisms included significant apoptosis induction demonstrated by upregulation of bax along with a reduction in angiogenesis demonstrated by downregulation of VEGF. This was accompanied by inhibition of cell cycle progression mediated by upregulated p53 and downregulated PCNA and cyclin D1.

scholarly journals Exploring the clinical value of preoperative serum gamma-glutamyl transferase levels in the management of patients with hepatocellular carcinoma receiving postoperative adjuvant transarterial chemoembolization

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiao Ke ◽  
Fu Xiang ◽  
Chunhong Xiao ◽  
Qizhen Huang ◽  
Xiaolong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Transarterial Chemoembolization ◽  
Radical Resection ◽  
Gamma Glutamyl Transferase ◽  
Clinical Value ◽  
Gamma Glutamyl ◽  
Preoperative Serum ◽  
Before And After ◽  
Glutamyl Transferase

Abstract Background Preoperative serum gamma-glutamyl transferase (γ-GT) levels is significantly related to the prognosis of hepatocellular carcinoma (HCC), but its clinical value in the management of postoperative adjuvant transarterial chemoembolization (PA-TACE) has rarely been explored. This study aimed to investigate whether γ-GT levels could be taken as a biomarker to guide the management of PA-TACE in resectable HCC. Methods HCC patients receiving radical resection were identified through the primary liver cancer big data (PLCBD) from December 2012 to December 2015. Prognostic factors of overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate cox analyses, and subgroup analysis was conducted between PA-TACE group and non-TACE stratified by γ-GT levels before and after 1:1 propensity score matching (PSM). Results γ-GT level was found to be an independent risk factor of OS and DFS in 1847 HCC patients receiving radical resection (both P < 0.05), and patients with elevated γ-GT(> 54.0 U/L) have a shortened median OS and DFS, compared with those with normal γ-GT (both P < 0.001). In the subgroup of patients with normal γ-GT, there were no significant differences between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P > 0.05), and PA-TACE was not a significant prognostic factor of both OS and DFS before and after PSM (all P > 0.05). In the subgroup of patients with elevated γ-GT, significant differences were found between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P < 0.05), and PA-TACE was an independent prognostic factor of both OS and DFS (all P < 0.05). Conclusion Currently, we concluded that patients with more advanced HCC also have more elevated γ-GT, and these patients with elevated γ-GT would be benefited more from PA-TACE after radical resection.

scholarly journals Cyclin-Dependent Kinase Regulatory Subunit 2 Indicated Poor Prognosis and Facilitated Aggressive Phenotype of Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Jie Zhang ◽  
Qianqian Song ◽  
Jinxia Liu ◽  
Lina Lu ◽  
Yuqing Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Regulatory Subunit ◽  
Mrna Levels ◽  
Cyclin Dependent Kinase ◽  
Normal Tissues ◽  
Hcc Cells

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.

scholarly journals Long non-coding RNA LINC00641 promotes the growth and invasiveness of hepatocellular carcinoma by antagonizing miR-501-3p

2021 ◽  
Author(s):  
Haitao Xie ◽  
Hui Zhou ◽  
Yan Jiang ◽  
Wenqian Xu ◽  
Leping Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Proliferation And Invasion ◽  
Hcc Cells

IntroductionLong non-coding RNA LINC00641 has been reported to regulate tumor progression in several cancers. However, the expression and function of LINC00641 in hepatocellular carcinoma (HCC) is still unclear.Material and methodsIn this study, we measured the expression of LINC00641 in 79 pairs of HCC and adjacent normal liver tissues. The clinical significance of LINC00641 in HCC was explored. We also investigated the function of LINC00641 in HCC proliferation and invasion.ResultsWe observed that LINC00641 expression was significantly increased in HCC relative to normal tissues (P < 0.0001). High expression of LINC00641 was significantly associated with vascular invasion, advanced TNM stage, and reduced overall survival in HCC patients. Knockdown of LINC00641 inhibited the proliferation, colony formation, and invasion of HCC cells. In contrast, overexpression of LINC00641 promoted HCC cell growth and invasiveness. In vivo studies confirmed that knockdown of LINC00641 restrained tumorigenesis of HCC cells. Mechanistic studies revealed that LINC00641 inhibited the expression of miR-501-3p, which has been previously reported to act as a tumor suppressor in HCC. Furthermore, luciferase reporter assays validated that LINC00641 harbored a target site for miR-501-3p. Rescue experiments demonstrated that LINC00641-induced proliferation and invasion of HCC cells was reversed by co-expression of miR-501-3p.ConclusionsTaken together, LINC00641 contributes to aggressive phenotype of HCC cells by sponging miR-501-3p and represents a promising therapeutic target for this disease.

scholarly journals Serum gamma-glutamyl transferase to alanine aminotransferase ratio predict the vascular invasion and outcome in hepatitis B virus related hepatocellular carcinoma

2021 ◽  
Author(s):  
Zhifeng Zhao ◽  
Jiayun Lin ◽  
Xiaochun Ni ◽  
Hongjie Li ◽  
Lei Zheng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Subgroup Analysis ◽  
Alanine Aminotransferase ◽  
Vascular Invasion ◽  
Gamma Glutamyl Transferase ◽  
B Virus ◽  
Glutamyl Transferase

Abstract Backgrounds: The ratio of gamma-glutamyl transferase (GGT) to alanine aminotransferase (ALT) is a predictive biomarker for hepatitis and hepatocellular carcinoma (HCC). In this study, the relationship between GGT/ALT ratio and vascular invasion was explored in hepatitis B virus (HBV)-related HCC and tumor prognosis. Methods: Totally 558 patients were involved in this study. Univariate and multivariate logistic analysis were used to evaluate GGT/ALT as the risk factor of vascular invasion. Prognostic value of GGT/ALT was investigated by univariate and multivariate Cox analysis combined with Kaplan Meier curves. In order to reduce confounding bias, subgroup analysis and propensity score matching (PSM) were performed. Results: Patients were divided into high and low GGT/ALT groups with an optimal cut-off value of 2.95 in predicting vascular invasion. In univariate and multivariate logistic regression, high GGT/ALT group was listed as the independent risk factors for vascular invasion(P=0.03), the other risk factors included age (P=0.001), α-fetoprotein (AFP) (P=0.026), tumor size (P<0.001), tumor capsule (P=0.018), pathological differentiation (P<0.001) and Barcelona Clinic Liver Cancer (BCLC) classification (P<0.001). In survival analysis, high GGT/ALT ratio was associated with decreased overall survival (OS) (HR: 1.38; 95% CI: 1.03, 1.87; P<0.0001) and disease-free survival (DFS) rates (HR: 1.32; 95% CI: 1.03, 1.87; P<0.0001). In sensitivity analysis, comparable results were furtherly confirmed by subgroup analysis. In PSM analysis, GGT/ALT was still associated with vascular invasion independently (OR, 186; 95% CI, 1.23, 3.33). Conclusion: Preoperative GGT/ALT has good predictive value for vascular invasion, tumor severity and outcome in HBV-related HCC patients.

scholarly journals MicroRNA-361-5p Inhibits Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma

2016 ◽  
Vol 38 (2) ◽  
pp. 777-785 ◽  
Author(s):  
Jian-Jun Sun ◽  
Guo-Yong Chen ◽  
Zhan-Tao Xie
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nude Mice ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Western Blots ◽  
Normal Tissues ◽  
Proliferation And Invasion ◽  
Hcc Cells

Background/Aims: A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC). Methods: Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo. Results: miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice. Conclusion: Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients.

scholarly journals Can gamma-glutamyl transferase levels contribute to a better prognosis for patients with hepatocellular carcinoma?

2014 ◽  
Vol 8 (3) ◽  
pp. 134-138 ◽  
Author(s):  
Zhigang Wang ◽  
Peipei Song ◽  
Jufeng Xia ◽  
Yoshinori Inagaki ◽  
Wei Tang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gamma Glutamyl Transferase ◽  
Gamma Glutamyl ◽  
Glutamyl Transferase

scholarly journals Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cells apoptosis by reducing HIF-1α/mTOR mediated autophagy

2020 ◽  
Author(s):  
Fenfen Hong ◽  
Yu Gao ◽  
Yang Li ◽  
Linfeng Zheng ◽  
Feng Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Disease Free Survival ◽  
Cell Counting ◽  
Normal Tissues ◽  
Rna Transfection ◽  
Normal Hepatocyte ◽  
Incidence And Mortality ◽  
Cell Progression ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC, and to explore its related mechanisms. Methods: The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cells apoptosis was induced by nutrient-deficient culture medium, and detected by Cell Counting Kit‐8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection. Results: HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage and lymph node metastasis. Compared with low HIF1A-AS1 group, high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines, and was increased with the prolongation of nutrient-free culture. inhibition of HIF1A-AS1 promoted starvation-induced HCC cells apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cells autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition. Conclusions: HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cells apoptosis by reducing HIF-1α/mTOR mediated autophagy, promoting HCC cell progression. Trial registration: This research is retrospectively registered.

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