The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role o...The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.展开更多
BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To invest...BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To investigate the role of TRP genes in HCC,their association with HCC development and treatment was examined.METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database,and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum.Based on these analyses,clinically relevant TRP family genes were selected,and the association between the key TRP canonical type 1(TRPC1)gene and HCC patient prognosis was evaluated.RESULTS In total,28 TRP family genes were screened for clinical relevance,with multivariate analyses ultimately revealing three of these genes(TRPC1,TRP cation channel subfamily M member 2,and TRP cation channel subfamily M member 6)to be significantly associated with HCC patient prognosis(P<0.05).These genes were utilized to establish a TRP-related risk model.Patients were separated into low-and high-risk groups based on the expression of these genes,and high-risk patients exhibited a significantly poorer prognosis(P=0.001).Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways.TRPC1 was identified as a candidate gene in this family worthy of further study,with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes.Consistently,quantitative,immunohistochemistry,and western blot analyses revealed increased TRPC1 expression in HCC.CONCLUSION These three TRP genes help determine HCC patient prognosis,providing insight into tumor immune status and immunological composition.These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.展开更多
AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calci...AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calcium phosphate transfection method. Some metastasis-related parameters were detected in vitro, including adhesion assay, migration assay, expression of collagenase IV(c IV ase) and epidermal growth factor receptor (EGFR). RESULTS: The abilities of H-ras-transfected cell clones in adhesion to laminin (LN) or fibronectin (FN), migration, c IV ase secretion increased markedly, and the expression of EGFR elevated moderately. More importantly, these alterations were consistent positively with the expression of p21, the protein product of H-ras oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC cell in vitro to raise its metastatic potential.展开更多
Objective: Transforming Growth Factor-β1 (TGF-β1)plays a central role in the process of . growth suppressionof the hepatocytes, and its type II receptor (TGF-β1R II)transfers the signal of growth suppression. In th...Objective: Transforming Growth Factor-β1 (TGF-β1)plays a central role in the process of . growth suppressionof the hepatocytes, and its type II receptor (TGF-β1R II)transfers the signal of growth suppression. In this study,the gene expression of TGF-β1R II in HCC and itsclinical significance was investigated. Methods: Theexpression of TGF-β1R II mRNA in 30 cases Of HCCtissue and the surrounding liver tissue was separatelydetected using reverse transcription-PCR. Results:The positive expression rate of TGF-β1R II mRNA wassignificantly lower in HCC tissue (11/30) than that in thesurrounding liver tissue (23/30) (P<0.01). Further, theless the cancer tissue expressed TGF-β1R II mRNA, themore poorly the tumoral hepatocyte differentiated(P<0.01) and the more portal vein cancer embolusexisted (p=0.0465). Conclusion: The decreaseexpression of TGF-β1 R II mRNA by tumoral hepatocyteresults in the defect of its negative growth regulation,and this may be one of the most important reasons forits carcinogenesis and uncontrolled growth.展开更多
INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabi...INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabilizing the phenotype of cell.DNA methylation status reduction and/or patternalteration are related to activation and abnormallyhigh expression of some oncogenes and cellularmalignancy[1-6]. c-fms oncogene encodes for colonystimulating factor 1 receptor (CSF-1R)[7], c-fms/CSF-1R was highly expressed in hepatocellularcarcinoma (HCC) tissue, but the mechanismremained obscure[8,9].展开更多
AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （...AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （HCC） versus colorectal liver metastases （CRLM） and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS： Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS： Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION： Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.展开更多
Receptor mediated gene delivery is a new gene transfer strategy. Asialoglycoprotein receptor (ASGP-R), the receptor of asialoorosomucoid (Asor), is specially expressed on the surface of hepatocyte. In this paper, the ...Receptor mediated gene delivery is a new gene transfer strategy. Asialoglycoprotein receptor (ASGP-R), the receptor of asialoorosomucoid (Asor), is specially expressed on the surface of hepatocyte. In this paper, the nuclide 131I was combined with Asor to form a kind of soluble nuclide-protein complex, which can be specifically endocytosed into hepatocyte by ASGP-R. After intravenous injection of the complex into experimental animals, the deposition of Asor in vivo and the targeting quality of hepatocyte was detected by ECT. This research testified the feasibility of targeting Asor complex delivery to hepatocyte mediated by ASGP-R in vivo, and provided foundation for the genetic diagnosis and gene therapy of hepatic cell-related diseases.展开更多
目的:观察干扰胰岛素样生长因子-Ⅰ型受体(insulin-like growth factor-Ⅰreceptor,IGF-ⅠR)表达对肝癌(PLC/PRF/5及Bel-7404)细胞增殖、周期、凋亡的影响及联合抗癌、靶向药物抑制细胞增殖的协同作用.方法:设计与合成多条针对IGF-ⅠR...目的:观察干扰胰岛素样生长因子-Ⅰ型受体(insulin-like growth factor-Ⅰreceptor,IGF-ⅠR)表达对肝癌(PLC/PRF/5及Bel-7404)细胞增殖、周期、凋亡的影响及联合抗癌、靶向药物抑制细胞增殖的协同作用.方法:设计与合成多条针对IGF-ⅠR序列的shRNA,插入pGPU6/GFP/Neo载体,构建、转染肝癌细胞株、筛选高效质粒,观察沉默IGF-ⅠR表达对肝癌细胞增殖的抑制作用与机制.结果:4对构建IGF-ⅠR-shRNA经筛选以s h R N A 4干扰效果最佳且具特异性;以shRNA4转染效率PLC/PRF/5细胞为71%和Bel-7404细胞为90%;在mRNA水平上抑制率前者为59.6%±2.8%,后者为54.9%±2.6%;蛋白水平上IGF-ⅠR表达均同步减少;转染72h后,PLC/PRF/5细胞增殖抑制率为63.87%±3.90%(t=19.244,P<0.001)及Bel-7404细胞为61.47%±1.70%(t=5.493,P<0.005),均呈时间依赖性,且增殖周期发生G1期阻滞,细胞周期蛋白(CyclinD1)表达受抑,细胞凋亡增加;shRNA4增加肝癌细胞对靶向药物索拉非尼及化疗药物奥沙利铂的敏感性.结论:下调IGF-ⅠR基因转录可抑制肝癌细胞增殖、诱导凋亡,改善肝癌细胞对靶向药物及化疗药物敏感性,提示IGF-ⅠR有望成为肝癌基因治疗的有效靶点.展开更多
文摘The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.
基金Supported by National Natural Science Foundation of China,No.82260535National Natural Science Foundation of Guizhou Medical University Hospital Incubation Program,No.gyfynsfc-2022-07.
文摘BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To investigate the role of TRP genes in HCC,their association with HCC development and treatment was examined.METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database,and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum.Based on these analyses,clinically relevant TRP family genes were selected,and the association between the key TRP canonical type 1(TRPC1)gene and HCC patient prognosis was evaluated.RESULTS In total,28 TRP family genes were screened for clinical relevance,with multivariate analyses ultimately revealing three of these genes(TRPC1,TRP cation channel subfamily M member 2,and TRP cation channel subfamily M member 6)to be significantly associated with HCC patient prognosis(P<0.05).These genes were utilized to establish a TRP-related risk model.Patients were separated into low-and high-risk groups based on the expression of these genes,and high-risk patients exhibited a significantly poorer prognosis(P=0.001).Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways.TRPC1 was identified as a candidate gene in this family worthy of further study,with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes.Consistently,quantitative,immunohistochemistry,and western blot analyses revealed increased TRPC1 expression in HCC.CONCLUSION These three TRP genes help determine HCC patient prognosis,providing insight into tumor immune status and immunological composition.These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.
文摘AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calcium phosphate transfection method. Some metastasis-related parameters were detected in vitro, including adhesion assay, migration assay, expression of collagenase IV(c IV ase) and epidermal growth factor receptor (EGFR). RESULTS: The abilities of H-ras-transfected cell clones in adhesion to laminin (LN) or fibronectin (FN), migration, c IV ase secretion increased markedly, and the expression of EGFR elevated moderately. More importantly, these alterations were consistent positively with the expression of p21, the protein product of H-ras oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC cell in vitro to raise its metastatic potential.
文摘Objective: Transforming Growth Factor-β1 (TGF-β1)plays a central role in the process of . growth suppressionof the hepatocytes, and its type II receptor (TGF-β1R II)transfers the signal of growth suppression. In this study,the gene expression of TGF-β1R II in HCC and itsclinical significance was investigated. Methods: Theexpression of TGF-β1R II mRNA in 30 cases Of HCCtissue and the surrounding liver tissue was separatelydetected using reverse transcription-PCR. Results:The positive expression rate of TGF-β1R II mRNA wassignificantly lower in HCC tissue (11/30) than that in thesurrounding liver tissue (23/30) (P<0.01). Further, theless the cancer tissue expressed TGF-β1R II mRNA, themore poorly the tumoral hepatocyte differentiated(P<0.01) and the more portal vein cancer embolusexisted (p=0.0465). Conclusion: The decreaseexpression of TGF-β1 R II mRNA by tumoral hepatocyteresults in the defect of its negative growth regulation,and this may be one of the most important reasons forits carcinogenesis and uncontrolled growth.
基金Supported by the Natural Science Foundation of Guangdong Province, No 990422
文摘INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabilizing the phenotype of cell.DNA methylation status reduction and/or patternalteration are related to activation and abnormallyhigh expression of some oncogenes and cellularmalignancy[1-6]. c-fms oncogene encodes for colonystimulating factor 1 receptor (CSF-1R)[7], c-fms/CSF-1R was highly expressed in hepatocellularcarcinoma (HCC) tissue, but the mechanismremained obscure[8,9].
文摘AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （HCC） versus colorectal liver metastases （CRLM） and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS： Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS： Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION： Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.
基金This project was supported by a grant fromthe Hubei Natural Sciences Foundation (No .2001ABA004) .
文摘Receptor mediated gene delivery is a new gene transfer strategy. Asialoglycoprotein receptor (ASGP-R), the receptor of asialoorosomucoid (Asor), is specially expressed on the surface of hepatocyte. In this paper, the nuclide 131I was combined with Asor to form a kind of soluble nuclide-protein complex, which can be specifically endocytosed into hepatocyte by ASGP-R. After intravenous injection of the complex into experimental animals, the deposition of Asor in vivo and the targeting quality of hepatocyte was detected by ECT. This research testified the feasibility of targeting Asor complex delivery to hepatocyte mediated by ASGP-R in vivo, and provided foundation for the genetic diagnosis and gene therapy of hepatic cell-related diseases.
文摘目的:观察干扰胰岛素样生长因子-Ⅰ型受体(insulin-like growth factor-Ⅰreceptor,IGF-ⅠR)表达对肝癌(PLC/PRF/5及Bel-7404)细胞增殖、周期、凋亡的影响及联合抗癌、靶向药物抑制细胞增殖的协同作用.方法:设计与合成多条针对IGF-ⅠR序列的shRNA,插入pGPU6/GFP/Neo载体,构建、转染肝癌细胞株、筛选高效质粒,观察沉默IGF-ⅠR表达对肝癌细胞增殖的抑制作用与机制.结果:4对构建IGF-ⅠR-shRNA经筛选以s h R N A 4干扰效果最佳且具特异性;以shRNA4转染效率PLC/PRF/5细胞为71%和Bel-7404细胞为90%;在mRNA水平上抑制率前者为59.6%±2.8%,后者为54.9%±2.6%;蛋白水平上IGF-ⅠR表达均同步减少;转染72h后,PLC/PRF/5细胞增殖抑制率为63.87%±3.90%(t=19.244,P<0.001)及Bel-7404细胞为61.47%±1.70%(t=5.493,P<0.005),均呈时间依赖性,且增殖周期发生G1期阻滞,细胞周期蛋白(CyclinD1)表达受抑,细胞凋亡增加;shRNA4增加肝癌细胞对靶向药物索拉非尼及化疗药物奥沙利铂的敏感性.结论:下调IGF-ⅠR基因转录可抑制肝癌细胞增殖、诱导凋亡,改善肝癌细胞对靶向药物及化疗药物敏感性,提示IGF-ⅠR有望成为肝癌基因治疗的有效靶点.
