The Analyses Of Impact Factors Predicting Survival In Patients With Cholangiocarcinoma And The Correlation Between Cholangiocarcinoma And Inflammation

【objective】To review the clinical data and survival information of cholangiocarcinomapatients with cholangiocarcinoma operation, and to explore the relationship ofchinicopathological features, The local inflammatory cells in the tumormicroenvironment distribution with prognosis of these patients. To study theexpression of key proteins of inflammation-related signaling pathways in patientswith cholangiocarcinoma operations as well as discuss the relationship among theabove factors expression, chinicopathological features and prognosis. To predict thepatients’s risk of recurrence and metastasis and death of biomarkers to provide newtargets for cancer therapy in future.【Method】Clinical data and the completed follow-up information of cholangiocarcinomapatients who underwent cholangiocarcinoma operation from January2004toDecember2010were analyzed retrospectively the relationship of clinicopathologicalfeatures, neutrophils, macrophages, and progonosis of these patients. Expression ofc-met、mTOR、NF-κB p50were detected in surgical pathology specimens of thesepatients by immunohistochemistry to analysis the relationship of these markersexpression, clinicopathological features, and prognosis by SPSS19.0softwarepackage.【Result】1. All291patients included in the study were cholangiocarcinoma withcholangiocarcinoma operation. The median follow-up time was55.9months. Of the294patients,168patients (57.8%) had experienced tumor recurrence and metastasis,and222(76.3%) patients had died by the end of the follow-up date (September30, 2012). The median DFS was12.83months, and the median OS was21.20months.The1,3,5-year disease-free survival rate were62.6%,51.2%,16.3%respectively. The1,3,5-year overall survival rates were71.8%,38.1%,10.7%respectively.2. TNM stage, the degree of tumor differentiation, the preoperative level ofCA199, positive or negative margins are independment risk factors in predicting DFS.Tumor local recurrence, TNM stage, the preoperative level of CA199, intraoperativetransfusion, surgical approach, the degree of tumor differentiation, tumor location, thepreoperative level of alkaline phosphatase (ALP), are independment risk factors inpredicting OS.3. High CD15expression in cancer tissues than in adjacent tissues. In cancertissues with high expression of CD15was significantly shorter OS than lowexpression in CD15, the difference was statistically significant (P=0.008), CD15high expression were significantly shorter DFS than low expression in CD15, thedifference was statistically significant (P=0.029). By COX multivariate analysis,high expression CD15in cancer tissues was an independment risk factor in predictingOS approximately for patients with cholangiocarcinoma(P=0.012, RR=1.601).4. High CD68expression in adjacent tissues than in cancer tissues. In cancertissues with high expression of CD68was significantly longer OS than low expressionin CD68, the difference was statistically significant (P=0.009), But the value ofexpression of CD68have no influence on DFS. By COX multivariate analysis, lowexpression CD68in cancer tissues was an independment risk factor in predicting OSapproximately for patients with cholangiocarcinoma(P=0.001, RR=1.669).5. The high expression of c-met is an independent risk factors in predictingDFS(OR=1.427) and OS(OR=1.390). The high expression of mTOR is anindependent risk factors in predicting DFS (OR=1.743) and OS(OR=1.677). The hihgexpression of NF-κBp50is an independent risk factors in predicting OS(OR=1.948).6. Spearman rank correlation analysis showed that no correlation between c-metand mTOR, and c-met and NF-κBp50, mTOR and NF-κBp50having a correlationbetween each other. The DFS and OS of patients with c-met and mTORco-low-expression are obviously better than both or only one high-expression (P=0.000and0.000, respectively). The OS of patients with c-met and NF-κBp50co-low-expression are obviously better than both or only onehigh-expression(P=0.003). The OS of patients with mTOR and NF-κ Bp50co-low-expression are obviously better than both or only onehigh-expression(P=0.001). The DFS and OS of patients with c-met, mTOR and NF-κBp50co-low-expression are obviously better than both or only one high-expression ortwo high-expression (P=0.013and0.000, respectively), which can also be seen fromthe survival curves obvious trend.7. Spearman rank correlation analysis showed that c-met, mTOR, NF-κBp50berween CD15having a correlation, but c-met, mTOR, NF-κBp50berween CD68having no correlation. The DFS and OS of patients with c-met and CD15co-low-expression are obviously better than both or only one high-expression(P=0.003and0.002, respectively). The DFS and OS of patients with mTOR andCD15co-low-expression are obviously better than both or only onehigh-expression(P=0.000and0.000, respectively). The OS of patients with NF-κBp50and CD15co-low-expression are obviously better than both or only onehigh-expression(P=0.002). The co-expression of both states had no significant effecton DFS.【Conclusion】1. In this group of researchers, TNM stage, the degree of tumor differentiation,the preoperative level of CA199, positive or negative margin are independment riskfactors in predicting DFS. Tumor recurrence, TNM stage, the preoperative level ofCA199, intraoperative transfusion, surgical approach, the degree of tumordifferentiation, tumor location, the preoperative level of Alkaline phosphatase (ALP),are independment risk factors in predicting OS.2. Analysis of291cases of patients with cholangiocarcinoma tumormicroenvironment local inflammatory state. Univariate analysis CD15in cancertissues with high expression DFS and OS shorteer; CD68in cancer tissues with highexpression OS longer, DFS has no significant difference. Multivariate analysis incancer tissue, CD15high-expression is an independent risk factor for OS, CD68 low-expression is an independent risk factor for the OS.3. The inflammation-related molecules, c-met and mTOR having no correlation,and c-met and NF-κBp50, mTOR and NF-κBp50having a correlation between eachother. High-expression of c-met or mTOR or both c-met and mTOR co-high-expression or all c-met, mTOR and NF-κBp50co-high-ewpression is an independentrisk factor of DFS. Each of the three above either alone or both or all of theexpression is an independent risk factor of OS. The above indicators suggests thedirection and target therapy of cholangiocarcinoma, but further experiments to verify.4. The inflammation-related molecules and neutrophil-specific molecular marker,c-met, mTOR, NF-κBp50between CD15having a correlation, but c-met, mTOR,NF-κBp50between CD68having no correlation. c-met, mTOR, NF-κBp50betweenCD15co-high-expression is an independent risk factor of OS. c-met, mTOR,between CD15co-high-expression is an independent risk factor of DFS. The abovecorrelation can be associated with inflammation of the cholangiocarcinoma researchto make some contribution, but the mechanism is unclear, further studies are neededto validate.