Expression And Significance Of HMGB1 And NF-κB In Intrahepatic Lithiasis Associated With Intrahepatic Cholangiocarcinoma

Objective To investigate the expressions and clinical significance of HMGB1 and NF-κB in intrahepatic lithiasis associated with intrahepatic cholangiocarcinoma(IHCC),Relationship between the expression of HMGB1、NF-κB and the onset and progress of IHCC was investigated to lay an experimental base for the diagnosis and treatment of IHCC.Methods We enrolled the bile duct histopathologic wax blocks of liver tissues specimen of hepatectomy within 10 years(from 2004.1 to 2013.12).(1) Part I :from 2004.1 to2013.12, 110 bile duct histopathologic wax blocks were collected, 40 cases of hepatolithiasis associated with intrahepatic cholangiocarcinoma were considered as tumor group, 40 cases of intrahepatic biliary calculi by bile duct tissues wereconsidered as inflammatory group and 30 cases of normal bile duct tissues were considered as normal group(operations of hemangiomas of liver or liver traum).The SP method of Immune histochemical method was applied to analyze the expression of HMGB1 and NF- κ B and their relations with clinicopathologic factors and the accumulated survival rates in the organizations of group I.(2)Part II:from 2004.1 to2013.12. We enrolled 65 cases of intrahepatic cholangiocarcinoma tumor tissue, we used the same method to study the expression of HMGB1 and MVD in the sample.Results : Part I: 1.The positive rate of the expression of HMGB1 in tumor group 、inflammatory group、normal group was 67.5%、42.5%、20%;The expression rates of HMGB1 in tumor group were significant higher than that in inflammatory group and normal group(P<0.05). The HMGB1 expression was significantly associated with tumor differentiation、the depth of tumor invasion and the lymph node metastasis in patients of HCWC(P<0.05),while there were no significant relationship with gender and age( P>0.05).In patients with IHCC, the survival rate in cases with HMGB1-positive expression was significantly lower than those with HMGB1-negative expression(P<0.05).2.The positive rate of the expression of NF-κB in tumor group、 inflammatory group、normal group was 75%、50%、23.3%;The expression rates of NF-κB in tumor group were significant higher than that in inflammatory group and normal group( P<0.05). The NF-κ B expression showed no significant relationship with tumor differentiation、the depth of tumor invasion、the lymph node metastasis and gender 、age in patients with HCWC(P>0.05).In tumor group, the NF-κB expression exerted no impact on patients survival rate(P>0.05).3.The expression of HMGB1 was followed by a high expression of NF-κB in tumor group, the positive rate was considered as 92.6%. Spearman-related analysis showed a positive relationship the HMGB1 expression and NF- κ B expression in HCWC(r=0.586,P<0.05).4.Patients in tumor group: the survival rate of HMGB1-positive and NF- κB-positive group was significant lower than HMGB1-negative and NF- κ B-positive group( χ 2=9.933, P=0.01),and it showed no significant relationship with HMGB1-positive and NF-κB-negative(χ2=1.759,P=0.185),however, it is significant lower than HMGB1-negative and NF-κB-negative group(χ2=5.512,P=0.019).Part II: 1.The positive rate of the expression of HMGB1 was 58.5%; The HMGB1 expression was significantly associated with tumor differentiation、vessel invasion and the lymph node metastasis in patients of ICC(P<0.05),while there were no significant relationship with gender,age and tumor size(P>0.05).In patients with ICC, the survival rate in cases with HMGB1-positive expression was significantly lower than those with HMGB1-negative expression(P<0.05).2.The positive rate of the expression of HMGB1 was 49.2%;The HMGB1 expression was significantly associated with vessel invasion in patients of ICC(P<0.05),while there were no significant relationship with gender,age,tumor differentiation,tumor size and the lymph node metastasis(P>0.05).In patients with ICC, the survival rate in cases with MVD-positive expression was significantly lower than those with MVD-negative expression(P<0.05).3.Spearman-related analysis showed a positive relationship the HMGB1 expression and MVD expression in ICC(r=0.268,P=0.03).4.Patients in tumor group: the survival rate of HMGB1-positive and MVD-positive group was significant lower than HMGB1-negative and NF- κ B-positive group( χ2=5.979,P=0.014), lower than HMGB1-positive and MVD-negative(χ2=14.616,P < 0.01),lower than HMGB1-negative and MVD-negative group( χ2=4.017,P=0.045).Conclusion:1.The HMGB1/NF- κ B pathway probably participate in the process of occurrence and development of IHCC.2.There was a positive relationship the HMGB1 expression and NF-κB expression in IHCC.3.HMGB1 expression may exert a decisive impact on degree of malignancy of the tumor and prognosis of the patients.4.HMG1 expression and MVD were closely related to the vessel invasion and prognosis of intrahepatic cholangiocarcinoma.5.HMGB1 and MVD may potentially become one of the effective indicators for predicting vessel invasion in patients with intrahepatic cholangiocarcinoma.