| Part One:The Clinical Significance of T-cadherin and Arp2 Protein Expression in Patients with Intrahepatic Cholangiocarcinoma Objective:By analyzing the differences in the expression of T-cadherin and actin-associated protein 2(Arp2)in intrahepatic cholangiocarcinoma and paracancerous tissues,and to explore the correlation and clinical significance between the expression of the two proteins and the clinicopathological factors and prognosis of intrahepatic cholangiocarcinoma.Methods:32 postoperative paraffin specimens of intrahepatic cholangiocarcinoma and adjacent tissues and 4 fresh intrahepatic cholangiocarcinoma tissues were collected,and the prognostic data were obtained by following up the postoperative survival time.Immunohistochemical technique for T-cadherin and Arp2 was performed in paraffin embedded sections of those intrahepatic cholangiocarcinoma and adjacent tissues,and then to semi-quantitatively detect 4 cases of fresh intrahepatic cholangiocarcinoma and corresponding adjacent cancers by immunoblotting The expression levels of the two proteins in the tissue specimens were finally analyzed using statistical methods to explore the differences in the expression of the two proteins in different bile duct tissues and the relationship with the clinicopathological factors and prognosis of intrahepatic cholangiocarcinoma.Results:1.The weakening or deletion rate of T-cadherin cell membrane expression in intrahepatic cholangiocarcinoma(71.9%)was higher than that in adjacent normal bile duct tissue(34.4%),and the difference was statistically significant(P < 0.01).Western blot showed that the ratio of protein band to internal reference gray value in cancer tissue was 0.688(0.415 ～ 1.273),which was lower than that in paracancerous tissue2.581(1.647 ～ 3.265),and the difference was not statistically significant.2.The positive rate of Arp2 protein in cytoplasm and nucleus of intrahepatic cholangiocarcinoma(75.0%)was significantly higher than that of adjacent normal bile duct tissue(9.4%),and the difference was statistically significant(P < 0.01).Western blot showed that the ratio of the protein band to the internal reference gray value in cancer tissues was 0.673(0.515 ～ 0.835),which was higher than that in adjacent tissues0.500(0.415 ～ 0.575).The difference was not statistically significant.3.By analyzing the expression of T-cadherin and Arp2 protein and clinicopathological parameters of patients with intrahepatic cholangiocarcinoma,T-cadherin expression is related to tumor histopathological grade,TNM stage and lymph node metastasis factors(P<0.05);Overexpression is related to the histological grade of tumor tissue and the factors of TNM staging(P<0.05).4.In intrahepatic cholangiocarcinoma,the positive expression of T-cadherin membrane was negatively correlated with the positive expression of Arp2(r=-0.762,P<0.01).5.Kaplan-Meirer survival analysis showed that there was no significant difference in postoperative survival time between those with negative and positive expressions of T-cadherin and Arp2(P> 0.05).Conclusions:1.The expression of T-cadherin in intrahepatic cholangiocarcinoma is decreased or even deleted,and it is related to histopathological grade,TNM stage and lymph node metastasis,suggesting that its low expression may be related to the invasion and metastasis of intrahepatic cholangiocarcinoma.2.The high expression of Arp2 protein in intrahepatic cholangiocarcinoma is related to histopathological grade and TNM stage,suggesting that its high expression may be related to the invasion and metastasis of intrahepatic cholangiocarcinoma.3.There is a negative correlation between the expression of T-cadherin and Arp2 in intrahepatic cholangiocarcinoma,which may restrict each other in the occurrence and development of cholangiocarcinoma.Part Two:Survival Analysis of Stereotactic Radiotherapy Combined with Chemotherapy in the Treatment of Advanced Intrahepatic Cholangiocarcinoma Objective:To investigate the clinical efficacy of chemotherapy alone and stereotactic radiotherapy combined with chemotherapy in the treatment of advanced intrahepatic cholangiocarcinoma.Methods:In a retrospective cohort study,38 patients with advanced intrahepatic cholangiocarcinoma who had received stereotactic radiotherapy or chemotherapy were divided into two groups: simple chemotherapy group and stereotactic radiotherapy combined with chemotherapy group.The objective curative effect was evaluated by RECIST1.1 standard,and the effective rate,disease control rate,progression-free survival time and total survival time of the two regimens were compared and analyzed.Results:1.Among the 38 patients who met the inclusion criteria,there were 21 males and17 females,aged from 28 to 74 years old,with an average of(55.45±12.20)years old.There were 27 cases in simple chemotherapy group and 11 cases in stereotactic radiotherapy combined with chemotherapy group.2.All the 38 patients could evaluate the curative effect,and the median follow-up time was 9.0(95%CI:7.92-10.08)months.The effective rates of simple chemotherapy group and stereotactic radiotherapy combined with chemotherapy group were 14.81%(4/27)and 9.09%(1/11),respectively,and the disease control rates were 44.44%(12/27)and 27.27%(3/11),respectively.There was no significant difference in the effective rate and disease control rate between the two groups(P > 0.05).3.The median progression-free survival time(m PFS)of simple chemotherapy group and combined treatment group was 4(95%CI:1.807-6.193)months and5(95%CI:2.810-7.190)months,respectively.The median overall survival time(m OS)was 8.0(95%CI:7.039-8.961)months and 10.0(95%CI:8.492-11.508)months,respectively.There was no significant difference in PFS and OS between the two groups(P > 0.05).4.The influence of clinical baseline characteristics on progression-free survival was analyzed.The results showed that the m PFS in groups 0,1 and 2 were 4.07(95%CI:1.44-6.70),4.00(95%CI:1.44-8.58)months and 1.00 months,respectively.The difference of PFS between groups was statistically significant(P < 0.05).Multivariate analysis showed that ECOG score and tumor histological grade were independent prognostic factors of PFS.5.The influence of clinical baseline characteristics on overall survival was analyzed.The results showed that there was no significant difference in OS among clinical baseline groups.Conclusions:1.In this study,there was no significant difference in the efficacy of stereotactic radiotherapy combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced intrahepatic cholangiocarcinoma.2.ECOG2 and poor histological differentiation are independent risk factors for progression-free survival in patients with advanced intrahepatic cholangiocarcinoma. |
PDF Full Text Request