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.

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.

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.

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.

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.

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.

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.

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.

Objective:To investigate T cell epitope spectrum of alpha fetoprotein (AFP) restricted by 13 dominant human leukocyte antigen A (HLA-A) molecules in Chinese population.Methods:AFP T cell epitope candidates presented by 13 HLA-A molecules were in silico predicted using multiple epitope prediction algorithms. Then, the candidate epitope peptides were co-cultured in vitro with fresh peripheral blood mononuclear cells (PBMCs) from hepatocellular carcinoma (HCC) patients, followed by intracellular cytokine staining (ICS) and flow cytometry to verify the immunogenicity of the candidate epitope peptides. Peptide competition binding assay of HLA-A molecules were performed using 12 HMy2.CIR cell lines expressing the indicated HLA-A molecules to analyze the affinity and cross-restriction of candidate epitope peptides with HLA-A molecules. Results:PBMCs from 67 AFP + HCC patients were co-cultured in vitro with 42 candidate T cell epitope peptides, and the result showed that 20 epitope peptides stimulated CD8 + T cell responses (named as positive epitope peptides). Peptide competitive binding assay revealed 22 candidate epitope peptides with high affinity, 13 with inter affinity, six with low affinity, and 10 without affinity with indicated HLA-A molecules, respectively. The 20 positive epitope peptides presented high or inter affinity with corresponding HLA-A molecules and most of them displayed cross-binding properties with several HLA-A molecules. Conclusions:Twenty AFP-specific CD8 + T cell epitope peptides restricted by the predominant HLA-A molecules in Chinese population are obtained by the HCC patients-derived T-cell functional experiments, and the cross-binding ability of these epitope peptides to the corresponding HLA-A molecules is preliminary identified. These results provide systematic and fundamental data for the design of AFP-specific T cell detection systems and T cell epitope-based vaccines universal for the Chinese population.

OBJECTIVES: 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) staining 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 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, amino acid metabolism, etc. SIRT2 expression level was related to serum triglycerides level, tumor size and lymph node metastasis (all P<0.05). The survival analysis results showed that the patients with higher SIRT2 expression had a significant 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.