scholarly journals The correlation of fibrinogen-like protein-1 expression with the progression and prognosis of hepatocellular carcinoma

Author(s):  
Nanni Hua ◽  
Chen Yang ◽  
Anxian Chen ◽  
Yi Feng ◽  
Xianglei He ◽  
...  

Abstract Background ConclusionsFibrinogen-like protein-1 (FGL1), as the member of FREP superfamily, had been widely concerned as a major immune inhibitory ligand of LAG-3. Although FGL1 expression levels didn’t have significant difference in most of tumors via online data analysis, we found that it was down-regulated in liver cancer. Moreover, the correlation between FGL1 expression and the progression and prognosis of hepatocellular carcinoma (HCC) was still disputed. Methods In our study, firstly, we used bioinformatics analysis to define the expression profile and clinical significance of FGL1 in HCC. Then, we determined the FGL1 level in human HCC cell lines, tumor and normal liver tissues from HCC patients by western blot. Furthermore, tissue microassays were used to detect the expression of FGL1 through immunohistochemistry staining and verify whether FGL1 expression levels were associated with clinicopathological features of HCC patients. Results The results proved that FGL1 was down-regulated significantly in HCC cell lines and HCC tissues, corresponding with the results of our bioinformatics analysis. FGL1 expression levels in HCC were related to Edmondson grade and metastasis. Additionally, high FGL1 expression was related to better overall survival in HCC patients, indicating that the down-regulated FGL1 was correlated with poor prognosis and FGL1 might function as a tumor suppressor. Conclusions Taken together, expression levels of FGL1 may correlate with the progression and prognosis of HCC, and FGL1 could be a potential prognostic biomarker.

2021 ◽  
Author(s):  
Nanni Hua ◽  
Anxian Chen ◽  
Chen Yang ◽  
Hui Dong ◽  
Xianglei He ◽  
...  

Abstract Fibrinogen-like protein-1 (FGL1), as the member of FREP superfamily, had been widely concerned as a major immune inhibitory ligand of LAG-3. Although FGL1 expression levels didn’t have significant difference in most of tumors via online data analysis, we found that it was down-regulated in liver cancer. Moreover, the correlation between FGL1 expression and the progression and prognosis of hepatocellular carcinoma (HCC) was still disputed. In our study, firstly, we used bioinformatics analysis to define the expression profile and clinical significance of FGL1 in HCC. Then, we determined the FGL1 level in 9 human HCC cell lines and 11 pairs of tumor and normal liver tissues from HCC patients by western blot. Furthermore, tissue microassays were used to detect the expression of FGL1 through immunohistochemistry staining and verify whether FGL1 expression levels were associated with clinicopathological features of HCC patients or not. The results of the experiment proved that FGL1 was down-regulated significantly in HCC cell lines and HCC tissues, corresponding with the results of our bioinformatics analysis. FGL1 expression levels in HCC were related to Edmondson grade and metastasis. Additionally, high FGL1 expression was related to better overall survival in HCC patients, indicating that the down-regulated FGL1 was correlated with poor prognosis and FGL1 might function as a tumor suppressor. Taken together, expression levels of FGL1 may correlate with the progression and prognosis of HCC, and FGL1 could be a potential prognostic biomarker.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jian-Yao Wang ◽  
Xiang-Kun Wang ◽  
Guang-Zhi Zhu ◽  
Xin Zhou ◽  
Jun Yao ◽  
...  

Abstract Backgroud In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC). Methods The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database. Results Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44–2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05). Conclusions Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22147-e22147
Author(s):  
H. Ueda

e22147 Background: FIP200 protein is a newly identified protein, and recent report has shown that FIP200 interacts with p53 and inhibit progression and proliferation. Although expression of FIP200 has been confirmed in normal liver,the expression and function in human HCC is completely unknown. In this study, we examined expression of FIP200 in HCC cell lines and investigated the involvement of FIP200 in proliferation and apoptosis. We also examined expression of FIP200 using HCC tissues and the correlation between FIP200 expression and clinical outcome. Methods: The study was conducted using HCC cell lines (HepG2, HuH7, and Hep3B). P53 status in HepG2, HuH7 and Hep3B are wild type, mutant type and deficient types respectively. Expression of endogenous FIP200 was assessed by western blotting. To investigate antitumor function, we carried out BrdU incorporation assay with transfected FIP200. TUNEL was carried out for identification of apoptosis. We also reviewed 14 patients who had undergone initial liver resection for HCC. Immunohistochemistry analysis for FIP200 was performed and we investigated the FIP200 expression levels according to differentiation degree of HCC tissues. Results: Endogenous FIP200 was detected in all cell lines, and those expression levels were different among cell lines. Overexpression of FIP200 significantly decreased BrdU incorporation in HepG2 and HuH7 but not Hep3B. In the study of TUNEL, apoptosis was observed for p53 wild HepG2 transfected with FIP200. In Hep3B, there was no significant difference observed. As for clinical samples, FIP200 were detected in all HCC and non-HCC tissues. FIP200 expression levels in HCC tissues were decreased compared to non-HCC tissues. Furthermore, as differentiation degree poored, those expression levels were decreased in the same tissue as well as in the different tissue. Conclusions: Endogenous FIP200 was expressed in all cell line. Those expression levels were different according to p53 status. Our study demonstrated that FIP200 inhibit proliferation in HCC expressed p53, and induce apoptosis in p53 wild HCC but not p53 deficient HCC. Furthermore, the FIP200 expression levels were significantly associated with differentiation degree. These data suggest that FIP200 plays an important role in promoting tumor progression in HCC. No significant financial relationships to disclose.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng-Lin Xu ◽  
Wei-Qun Guan ◽  
Xue-Ying Wang

Abstract Background This study aimed to investigate the expression level of the GATA6 gene in different oral cancer cells. Methods In this study, we sub-cultured normal oral epithelial cell lines HOK, human tongue squamous cell carcinoma cell lines CAL-27 and SCC-4, and human salivary gland adenoid cystic carcinoma cell lines SACC-LM and SACC-83. Subsequently, we used reverse transcription-polymerase chain reaction RT-PCR and Western blot methods to detect the mRNA and the protein expressions of GATA6 in normal oral epithelial cells, human tongue squamous cell carcinoma cells, and human salivary gland adenoid cystic carcinoma cells. Results The results of this study showed that the mRNA expression levels of GATA6 in CAL-27, SCC-4, and SACC-LM cells were significantly increased when compared with the HOK cells. However, the mRNA expression level of GATA6 in the SACC-83 cells had no significant difference compared with the HOK cells. The protein expression levels of GATA6 in the SCC-4 and SACC-LM cells were, however, significantly increased whereas the protein expression levels of GATA6 in the CAL-27 and SACC-83 cells had no significant difference when compared with the HOK cells. Conclusion The GATA6 gene may be related to the occurrence and progression of certain oral cancers.


2021 ◽  
Vol 22 (8) ◽  
pp. 3956
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Hae June Lee ◽  
Kiwon Song

Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and -independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rongjie Zhang ◽  
Yan Chen ◽  
Ge Zhou ◽  
Baoguo Sun ◽  
Yue Li ◽  
...  

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.


2019 ◽  
Vol 47 (3) ◽  
pp. 1319-1329 ◽  
Author(s):  
Jian Zhang ◽  
Hai Ma ◽  
Liu Yang ◽  
Hongchun Yang ◽  
Zhenxing He

Objectives Overexpression of human trophoblast cell surface antigen 2 (Trop2) has been observed in many cancers; however, its roles in proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma (HCC) remain unclear. Thus, this study aimed to characterize the function of Trop2 in HCC. Methods Trop2 protein expression was detected by immunohistochemistry in HCC tissues. Cell proliferation, apoptosis, and invasion were respectively measured by CCK-8, flow cytometry, Transwell, and wound healing assays. Expression levels of epithelial–mesenchymal transition-related proteins and Trop2 protein in HCC cell lines were detected by western blotting after silencing of the TROP2 gene. Results Trop2 protein was highly expressed in HCC tissues and HCC cell lines. Trop2 mRNA and protein expression levels decreased in HepG2 and HCCLM3 cells after transfection with Trop2 siRNA. Silencing of the TROP2 gene in HepG2 and HCCLM3 cells strongly inhibited cell proliferation and migration, while enhancing cell apoptosis. Investigation of the molecular mechanism revealed that silencing of the TROP2 gene suppressed epithelial–mesenchymal transition of HepG2 and HCCLM3 cells. Conclusions The results of the present study may improve understanding of the role of Trop2 in regulation of cell proliferation and invasion, and may aid in development of novel therapy for HCC.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Miao Liu ◽  
Lingyao Du ◽  
Zhiliang He ◽  
Libo Yan ◽  
Ying Shi ◽  
...  

Aim.ERp57 is involved in virus induced endoplasmic reticulum stress (ERS) and plays an important role in tumorigenesis. This study aimed to find whether HBV infection altered ERp57 expression and whether ERp57 regulation was involved in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) genesis.Materials and Methods.HBV-HCC tissues, chronic hepatitis B (CHB) liver tissues, and normal liver tissues were acquired. ERp57 expressions in these tissues were detected through immunohistochemistry (IHC). And ERp57 expression in liver cell line L02, HBV replicative liver cell line L02-pHBV4.1, and HCC cell lines were detected through western blot for verification. Then medical data on patients providing HCC tissues were collected and analyzed along with ERp57 expression.Results.Higher ERp57 expression was found in HCC and CHB tissues (p<0.001). And HCC cell lines and L02-pHBV4.1 presented higher ERp57 expression as well. In patients, ERp57 expression showed significant differences between death and survival groups (p=0.037). And cumulative survival in patients with higher ERp57 (score⩾8.75) is significantly lower (p=0.009).Conclusion.Our study found increased expression of ERp57 in HBV-HCC. Such altered expression could be related to HBV infection and high ERp57 expression may lead to poor prognosis of HBV-HCC patients.


2021 ◽  
Vol 17 (1) ◽  
pp. 142-151
Author(s):  
Jingqi Liu ◽  
Ligang Chen ◽  
Jinshui Pan ◽  
Meiya Chen ◽  
Jingping Zhou ◽  
...  

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.


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