BACKGROUND The cellular prion protein(PrPC),traditionally associated with neurodegenerative disorders,plays an important role in cancer progression and metastasis by inhibiting apoptosis.AIM To investigate the influen...BACKGROUND The cellular prion protein(PrPC),traditionally associated with neurodegenerative disorders,plays an important role in cancer progression and metastasis by inhibiting apoptosis.AIM To investigate the influence of PrPC expression in cholangiocarcinoma(CCA)on patient outcomes following surgical resection.METHODS Patients who underwent curative surgical resection for either intrahepatic or hilar CCA were enrolled in this retrospective study.Based on the immunohistochemical staining results of the surgical specimens,patients were categorized into two groups:The low PrPC group(negative or 1+)and the high PrPC group(2+or 3+).Survival analyses,including overall survival and recurrence-free survival,were conducted using the Kaplan-Meier method and compared using the log-rank test.RESULTS In total,seventy-six patients diagnosed with CCA(39 with intrahepatic and 37 with hilar CCA)underwent curative hepatectomy from January 2011 to November 2021.Among these patients,38(50%)demonstrated high PrPC expression,whereas the remaining 38(50%)showed low expression of PrPC.During a median follow-up period of 31.2 months(range:1 to 137 months),the high PrPC group had a significantly shorter median overall survival than the low PrPC group(40.4 months vs 137.9 months,respectively;P=0.041).Moreover,the high PrPC group had a significantly shorter median recurrence-free survival than the low PrPC group(13.3 months vs 23.8 months,respectively;P=0.026).CONCLUSION PrPC expression is significantly associated with early recurrence and decreased survival period in CCA patients following surgical resection.Thus,PrPC may be used as a prognostic factor in treatment planning.展开更多
BACKGROUND Citrullination is a post-translational modification mediated by calcium-dependent peptidylarginine deiminases that results in notable changes in protein structure and function.Glial fibrillary acidic protei...BACKGROUND Citrullination is a post-translational modification mediated by calcium-dependent peptidylarginine deiminases that results in notable changes in protein structure and function.Glial fibrillary acidic protein(GFAP),which is highly vulnerable to peptidylarginine deiminases-mediated modification,has been found to be elevated in activated hepatic stellate cells,with GFAP-positive hepatic stellate cells and myofibroblasts accumulating within and around areas of hepatic fibrosis.Although recent studies have shown that the expression of citrullinated GFAP(cit-GFAP)increases during hepatic fibrosis,its expression pattern and functional roles in hepatocellular carcinoma(HCC)remain unclear.AIM To determine whether cit-GFAP expression influences the recurrence and survival of patients undergoing hepatic resection for HCC.METHODS We retrospectively analyzed 169 patients with HCC who underwent hepatic resection.Based on the immunohistochemical staining of resected specimens,the enrolled patients were stratified into two groups according to cit-GFAP expression:Low(-/1+)or high(2+/3+)levels of expression.Kaplan-Meier survival curves were constructed to assess overall survival and recurrence-free survival,and comparisons between groups were performed using the log-rank test.RESULTS The median follow-up duration was 33 months(range,1-183).High cit-GFAP expression,identified in 81 patients(48.2%),was significantly associated with male sex,hepatitis B virus positivity,and higher Edmonson-Steiner grade.No associations were found between age,diabetes,hypertension,cirrhosis,Child-Pugh classification,major portal vein invasion,hematological or biochemical parameters,tumor size,or number.Patients exhibiting high cit-GFAP expression demonstrated significantly poorer overall survival.Multivariate Cox analysis identified large tumor size(hazard ratio:2.967;95%confidence interval:1.097-8.024;P=0.032)and high cit-GFAP expression(hazard ratio:2.753;95%confidence interval:1.015-7.464;P=0.047)as independent predictors of poor postoperative survival.Although recurrence rates were high in patients with high cit-GFAP expression,the difference was not statistically significant.CONCLUSION Following curative resection in patients with HCC,high cit-GFAP expression may serve as a potential prognostic biomarker,although further validation through independent cohort studies is warranted.展开更多
基金Supported by National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2023-00213951.
文摘BACKGROUND The cellular prion protein(PrPC),traditionally associated with neurodegenerative disorders,plays an important role in cancer progression and metastasis by inhibiting apoptosis.AIM To investigate the influence of PrPC expression in cholangiocarcinoma(CCA)on patient outcomes following surgical resection.METHODS Patients who underwent curative surgical resection for either intrahepatic or hilar CCA were enrolled in this retrospective study.Based on the immunohistochemical staining results of the surgical specimens,patients were categorized into two groups:The low PrPC group(negative or 1+)and the high PrPC group(2+or 3+).Survival analyses,including overall survival and recurrence-free survival,were conducted using the Kaplan-Meier method and compared using the log-rank test.RESULTS In total,seventy-six patients diagnosed with CCA(39 with intrahepatic and 37 with hilar CCA)underwent curative hepatectomy from January 2011 to November 2021.Among these patients,38(50%)demonstrated high PrPC expression,whereas the remaining 38(50%)showed low expression of PrPC.During a median follow-up period of 31.2 months(range:1 to 137 months),the high PrPC group had a significantly shorter median overall survival than the low PrPC group(40.4 months vs 137.9 months,respectively;P=0.041).Moreover,the high PrPC group had a significantly shorter median recurrence-free survival than the low PrPC group(13.3 months vs 23.8 months,respectively;P=0.026).CONCLUSION PrPC expression is significantly associated with early recurrence and decreased survival period in CCA patients following surgical resection.Thus,PrPC may be used as a prognostic factor in treatment planning.
基金Supported by Korean Society of Gastroenterology funded by Korea Research Foundation of Internal Medicine,No.KSG-2022-02.
文摘BACKGROUND Citrullination is a post-translational modification mediated by calcium-dependent peptidylarginine deiminases that results in notable changes in protein structure and function.Glial fibrillary acidic protein(GFAP),which is highly vulnerable to peptidylarginine deiminases-mediated modification,has been found to be elevated in activated hepatic stellate cells,with GFAP-positive hepatic stellate cells and myofibroblasts accumulating within and around areas of hepatic fibrosis.Although recent studies have shown that the expression of citrullinated GFAP(cit-GFAP)increases during hepatic fibrosis,its expression pattern and functional roles in hepatocellular carcinoma(HCC)remain unclear.AIM To determine whether cit-GFAP expression influences the recurrence and survival of patients undergoing hepatic resection for HCC.METHODS We retrospectively analyzed 169 patients with HCC who underwent hepatic resection.Based on the immunohistochemical staining of resected specimens,the enrolled patients were stratified into two groups according to cit-GFAP expression:Low(-/1+)or high(2+/3+)levels of expression.Kaplan-Meier survival curves were constructed to assess overall survival and recurrence-free survival,and comparisons between groups were performed using the log-rank test.RESULTS The median follow-up duration was 33 months(range,1-183).High cit-GFAP expression,identified in 81 patients(48.2%),was significantly associated with male sex,hepatitis B virus positivity,and higher Edmonson-Steiner grade.No associations were found between age,diabetes,hypertension,cirrhosis,Child-Pugh classification,major portal vein invasion,hematological or biochemical parameters,tumor size,or number.Patients exhibiting high cit-GFAP expression demonstrated significantly poorer overall survival.Multivariate Cox analysis identified large tumor size(hazard ratio:2.967;95%confidence interval:1.097-8.024;P=0.032)and high cit-GFAP expression(hazard ratio:2.753;95%confidence interval:1.015-7.464;P=0.047)as independent predictors of poor postoperative survival.Although recurrence rates were high in patients with high cit-GFAP expression,the difference was not statistically significant.CONCLUSION Following curative resection in patients with HCC,high cit-GFAP expression may serve as a potential prognostic biomarker,although further validation through independent cohort studies is warranted.