1.Effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells in polycystic ovarian syndrome
Yanshe SHAO ; Xuemei XU ; Baoqin YANG ; Huijuan LI ; Xia JI
China Pharmacy 2025;36(2):185-190
OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells (KGN cells) in polycystic ovarian syndrome (PCOS) and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52, 1.04, 2.08 g/(kg·d)] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum, KGN cells were divided into control group (without any treatment), dehydroepiandrosterone (DHEA) group (treated with 50 μmol/L DHEA for 48 h), blank serum group (treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h) and medium-concentration of Siwutang medicated serum group (treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h). The number of autophagosomes was observed in each group, and protein expressions of pathway-related proteins [fructose-1, 6-bisphosphatase 1 (FBP1),mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR)], autophagy-related proteins [p62, microtubule-associated protein 1 light chain 3 (LC3)] and mRNA expression of FBP1 were also detected. The (transfected) cells were further divided into Siwutang group (treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA), Siwutang+si-NC group [negative control small interfering RNA (siRNA) transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group (FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration Siwutang medicated serum for 72 h). The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group, DHEA group exhibited an increase in the number of autophagosomes, an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR, as well as increases in protein and mRNA expressions of FBP1, and decreased protein expression of p62 (P<0.05). Compared to both DHEA group and blank serum group, the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes, a decrease in LC3-Ⅱ/LC3-Ⅰ, and increases in p-mTOR/mTOR, protein expression of p62, protein and mRNA expressions of FBP1 (P<0.05). After knocking down FBP1, compared with Siwutang+si-NC group, Siwutang+si-FBP1 group showed a significant decrease in cell viability, protein expression of p62 , protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR, and an increase in LC3-Ⅱ/LC3-Ⅰ (P<0.05). CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells, thus inhibiting autophagy of KGN cells.
2.Effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells in polycystic ovarian syndrome
Yanshe SHAO ; Xuemei XU ; Baoqin YANG ; Huijuan LI ; Xia JI
China Pharmacy 2025;36(2):185-190
OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells (KGN cells) in polycystic ovarian syndrome (PCOS) and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52, 1.04, 2.08 g/(kg·d)] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum, KGN cells were divided into control group (without any treatment), dehydroepiandrosterone (DHEA) group (treated with 50 μmol/L DHEA for 48 h), blank serum group (treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h) and medium-concentration of Siwutang medicated serum group (treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h). The number of autophagosomes was observed in each group, and protein expressions of pathway-related proteins [fructose-1, 6-bisphosphatase 1 (FBP1),mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR)], autophagy-related proteins [p62, microtubule-associated protein 1 light chain 3 (LC3)] and mRNA expression of FBP1 were also detected. The (transfected) cells were further divided into Siwutang group (treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA), Siwutang+si-NC group [negative control small interfering RNA (siRNA) transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group (FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h, and then with 10% medium-concentration Siwutang medicated serum for 72 h). The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group, DHEA group exhibited an increase in the number of autophagosomes, an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR, as well as increases in protein and mRNA expressions of FBP1, and decreased protein expression of p62 (P<0.05). Compared to both DHEA group and blank serum group, the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes, a decrease in LC3-Ⅱ/LC3-Ⅰ, and increases in p-mTOR/mTOR, protein expression of p62, protein and mRNA expressions of FBP1 (P<0.05). After knocking down FBP1, compared with Siwutang+si-NC group, Siwutang+si-FBP1 group showed a significant decrease in cell viability, protein expression of p62 , protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR, and an increase in LC3-Ⅱ/LC3-Ⅰ (P<0.05). CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells, thus inhibiting autophagy of KGN cells.
3.Summary of the best evidence of accelerated rehabilitation nursing in perioperative period of patients undergoing hip and knee arthroplasty
Huiling WANG ; Hui LI ; Bing SHAO ; Ning HAN ; Yang SHEN ; Xianan SONG ; Zhengang JI
Chinese Journal of Practical Nursing 2024;40(2):110-117
Objective:To search, evaluate and summarize the best evidence summary of perioperative accelerated rehabilitation nursing for patients undergoing hip and knee arthroplasty, so as to provide reference for clinical perioperative nursing.Methods:Evidence-based nursing methods were used to search for relevant databases such as BMJ Best Practice, UpToDate, PubMed, CINAHL, and CNKI, etc.. The search period was from December 2010 to December 2022. Four researchers independently evaluated the quality of the guidelines, and two researchers independently evaluated the quality of expert consensus and system evaluation. Finally, the included literature was summarized.Results:A total of 12 pieces of literature, 3 guidelines, 5 expert consensus and 4 systematic reviews were included. From 13 aspects of preoperative education, preoperative optimization, anesthesia management, perioperative blood management, perioperative pain management, perioperative fluid management, perioperative temperature protection, infection prevention, thrombus prevention, postoperative nausea and vomiting, postoperative drainage, functional exercise, and perioperative rehabilitation promotion, 35 pieces of the best evidence for hip and knee replacement patients to accelerate rehabilitation nursing in the perioperative period was summarized.Conclusions:This study summarizes the best evidence of accelerated rehabilitation nursing in the perioperative period of hip and knee arthroplasty, aiming to build and standardize the accelerated rehabilitation nursing scheme in the perioperative period of hip and knee arthroplasty, so as to provide reference for clinical perioperative nursing.
4.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
5.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
6.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
7.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
8.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
9.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
10.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.

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