HMGB1和KLF7在胆囊癌组织中的表达及其与胆囊癌患者根治术后预后的关系OA

Objective To investigate the expression of high mobility group B1(HMGB1)and Krüppel like factor 7(KLF7)in gallbladder carcinoma(GBC)tissue,and their relationship with clinical pathological characteristics and prognosis of GBC patients after radical cholecystectomy.Methods Clinical data of 106 GBC patients,who underwent radical cholecystectomy in No.215 Hospital of Shaanxi Nuclear Industry from February 2018 to March 2020,were retrospectively analyzed.Immunohistochemistry was used to detect the protein expression of HMGB1 and KLF7 in GBC tissue and adjacent tissues.Spearman rank correlation analysis was used to analyze the correlation between HMGB1 and KLF7 expression.The Kaplan-Meier method was used to analyze the relationship of expression of HMGB1 and KLF7 with the prognosis of GBC patients after radical cholecystectomy.Cox regression was used to analyze the influencing factors of prognosis in GBC patients after radical cholecystectomy.Gallbladder carcinoma BGC-SD cells were cultured in vitro,and the mRNA expression levels of HMGB1 and KLF7 in the blank control group(Control group),negative interference control group(sh-NC group),HMGB1 knockdown group(sh-HMGB1 group),HMGB1 knockdown+empty vector group(sh-HMGB1+pc-NC group),and HMGB1 knockdown+KLF7 over-expression group(sh-HMGB1+pc-KLF7 group)were detected by RT qPCR.The survival of cells in each group was detected by the CCK8 method,and the migration and invasion in each group of cells were detected by the Transwell experiment.Results The positive expression rate of HMGB1 and KLF7 in GBC tissues was higher than those in adjacent carcinoma tissues,respectively(66.04%vs 33.96%,χ2=21.811,P<0.05;64.15%vs 35.85%,χ2=16.981,P<0.05).The expression of HMGB1 and KLF7 was related to the TNM stage,lymph node metastasis,infiltration of the common bile duct,and degree of tissue differentiation in GBC patients,and the differences are statistically significant(P<0.05).There was an obvious positive correlation between HMGB1 and KLF7 expression in GBC patients(r=0.544,P<0.05).Kaplan-Meier analysis showed that the 3-year overall survival rate of GBC patients with positive HMGB1 and KLF7 expression was lower than those of patients with negative expression(52.86%vs 77.78%,χ2=6.959,P<0.05;51.47%vs 78.95%,χ2=8.225,P<0.05).Multivariate Cox regression analysis showed that TNM Ⅲ stage(HR=2.803,95%CI 1.252 to 6.273,P=0.012),common bile duct infiltration(HR=1.147,95%CI 1.032 to 1.275,P=0.012),low tissue differentiation(HR=1.366,95%CI 1.256 to 1.486,P<0.001),lymph node metastasis(HR=4.195,95%CI 2.414 to 7.291,P<0.001),positive expression of HMGB1(HR=1.291,95%CI 1.037 to 1.608,P=0.023),and positive expression of KLF7(HR=2.017,95%CI 1.107 to 3.674,P=0.022)were all risk factors for death of GBC patients after radical cholecystectomy.The results of in vitro cell experiments showed that,compared with the Control group and sh-NC group,HMGB1,KLF7 mRNA expression levels,cell survival rate,cell migration and invasion number in the sh-HMGB1 group were decreased(P<0.05).Compared with sh-HMGB1 group and sh-HMGB1+pc-NC group,the KLF7 mRNA expression levels,cell survival rate,migration number and invasion number in sh-HMGB1+pc-KLF7 group were increased(P<0.05).Down-regulation of HMGB1 expression could inhibit the malignant biological characteristics of GBC cells,while over-expression of KLF7 could reverse the inhibitory effect of low expression of HMGB1 on the malignant phenotype of GBC cells.Conclusion HMGB1 and KLF7 are highly expressed in carcinoma tissues of GBC patients,and positive expression of HMGB1 and KLF7 may promote the poor prognosis of GBC.