La-related蛋白1在胆囊癌疾病进展中作用的研究

The role of La-related protein 1 in the progression of gallbladder cancer

目的探讨La-related蛋白1(LARP1)在胆囊癌疾病进展中的作用及其意义。方法收集行胆囊癌根治术的胆囊癌组织标本76例,胆囊腺瘤行胆囊切除术的胆囊腺瘤组织标本27例和肝血管瘤联合胆囊切除的胆囊组织标本21例。用免疫组化的方法检测石蜡标本中LARP1的表达水平,统计分析3组组织标本中LARP1的表达差异以及LARP1与胆囊癌患者临床病理资料和预后的关系。结果非疾病胆囊、胆囊腺瘤、胆囊癌3组LARP1表达的平均光密度分别为0.166(0.157,0.192)、0.219(0.185,0.281)、0.294(0.217,0.368);3组间LARP1表达的平均光密度差异有统计学意义(χ2=48.076,P<0.001);胆囊癌组与胆囊腺瘤组或非疾病胆囊组间差异均有统计学意义(P<0.001),胆囊腺瘤组与非疾病胆囊组间差异有统计学意义(Z=-3.118,P=0.002)。②进展期(TNMⅡ-ⅢB)胆囊癌组织中的LARP1表达水平显著高于早期(TNM 0-Ⅰ期)胆囊癌组织中的LARP1表达水平(Z=-2.361,P=0.018),并且胆囊癌组织中的LARP1表达水平和肿瘤的组织学分级相关(Z=-2.849,P=0.004)。③52例胆囊癌患者获得完整随访资料。进一步的Kaplan-Meier分析显示胆囊癌组中LARP1高表达亚组的术后生存期明显短于LARP1低表达亚组(Log Rank=7.132,P=0.008);TNMⅡ-ⅢB胆囊癌亚组的术后生存期明显短于TNM 0-Ⅰ期胆囊癌亚组(Log Rank=18.972,P<0.001)。单因素及多因素分析结果显示LARP1表达水平是胆囊癌患者的独立预后因素[HR=2.552,95%CI(1.235,5.271),P=0.011]。结论LARP1在非疾病胆囊、胆囊腺瘤、胆囊癌中的表达呈进行性升高;LARP1表达水平与胆囊癌TNM分期及组织分级呈正相关;LARP1表达水平与胆囊癌患者的预后相关。

Objective To investigate the role and significance of La-related protein 1(LARP1)in gallbladder cancer progression.Methods We selected 76 cases of gallbladder cancer tissue specimens underwent radical cholecystectomy,27 cases of gallbladder adenoma tissue specimens underwent cholecystectomy,and 21 cases of gallbladder tissue specimens underwent hepatectomy and cholecystectomy for hepatic hemangioma.The expression level of LARP1 in paraffin samples was detected by immunohistochemistry,and the difference of LARP1 expression in tissue samples of three groups was statistically analyzed,as well as the relationship between LARP1 andclinicopathological data and prognosis of patients with gallbladder cancer.Results①The average optical density of LARP1 expression in three groups of non-disease gallbladder,gallbladder adenoma and gallbladder cancer were 0.166(0.157,0.192),0.219(0.185,0.281)and 0.294(0.217,0.368),respectively.There was significant difference in average optical density of LARP1 expression among three groups(χ2=48.076,P≤0.001).There were statistically significant differences between the gallbladder cancer group and the gallbladder adenoma group or the gallbladder non-disease group(P<0.001),and there was statistically significant difference between the gallbladder adenoma group and the gallbladder non-disease group(Z=-3.118,P=0.002).②The expression level of LARP1 in advanced(TNMⅡ-ⅢB)gallbladder cancer tissues was significantly higher than that in early(TNM 0-Ⅰ)gallbladder cancer tissues(Z=-2.361,P=0.018),and the expression level of LARP1 in gallbladder cancer tissues was correlated with the histological grade of the tumor(Z=-2.849,P=0.004).③The complete follow-up data were obtained for 52 patients with gallbladder cancer.Further Kaplan-Meier analysis showed that the postoperative survival period of the LARP1 high-expression subgroup in the gallbladder cancer group was significantly shorter than that of the LARP1 low-expression subgroup(Log Rank=7.132,P=0.008).The survival time of progress(TNM stageⅡ-ⅢB)gallbladder cancer subgroup was obviously shorter than the early(TNM stage 0-Ⅰ)gallbladder subgroup(Log Rank=18.972,P<0.001).Furthermore,univariate and multivariate analyses showed that LARP1 expression level was an independent prognostic factor for patients with gallbladder cancer[HR=2.552,95%CI(1.235,5.271),P=0.011].Conclusion The expression of LARP1 in non-disease gallbladder,gallbladder adenoma and gallbladder cancer shows a progressive increase.The expression level of LARP1 is positively correlated with gallbladder cancer TNM stage and tissue grade.The expression level of LARP1 is correlated with the prognosis of gallbladder cancer patients.