【作者】 吴越；

【导师】 徐三荣；

【作者基本信息】 江苏大学 ， 外科学， 2023， 硕士

【摘要】 目的探究重组人序列相似性家族189,成员B(Family with sequence similarity189,member B,FAM189B),又称COTE 1在肝细胞癌组织中的表达情况及与肝细胞癌患者预后的关系,为肝细胞癌的临床治疗和预防提供参考依据。方法本次回顾性研究实验,纳入了2009年01月到2014年01月在江苏大学附属医院普外科行外科手术治疗的59例原发性肝细胞癌患者,收集其肝癌组织及相对应的癌旁组织(据肿瘤边缘2cm以上),采用QRT-PCR法检测癌组织及临近非肝癌组织中COTE 1 m RNA的表达量,同时利用免疫组化学检测59例肝癌患者癌组织及临近非肝癌组织中COTE 1蛋白的表达,将其分为低表达组及高表达组,同时收集患者完整的临床病理资料(年龄、性别、血清AFP值、肿瘤大小、HBs Ag表达情况)及术后随访信息(术后总生存时间及复发情况),分析COTE 1的表达水平与临床病理参数及患者预后的关系。结果(1)用免疫组化法检测59例肝癌患者癌组织及临近非肝癌组织中COTE 1蛋白的表达,癌组织中有37例COTE 1为高表达,占62.7%,癌旁组织中有24例COTE 1为高表达,肝癌组织中COTE 1的表达高于癌旁组织(P=0.017<0.05)。用QRT-PCR及Western blot法检测59例肝癌患者的癌组织和临近非肝癌组织中COTE1表达水平,结果显示,在肝癌组织中COTE1 m RNA和蛋白表达量高于临近非肝癌组织(P<0.01)。(2)COTE 1与年龄无相关性(r=0.081,P=0.542);COTE 1与AFP表达的呈正相关性(r=0.706,P<0.001);COTE 1与肿瘤大小无相关性(r=0.205,P<0.119)。按照免疫组化评分,将肝细胞癌患者分为COTE 1高表达组(>4分),COTE 1低表达组(0到4分)。不同性别之间的免疫组化评分没有统计学差异(Z=-1.002,P=0.320);HBs Ag阳性与阴性组之间的免疫组化评分没有统计学差异(Z=-0.514,P=0.607);肿瘤复发与未复发组间的免疫组化评分有统计学差异(Z=-2.425,P=0.042)。(3)用单因素和多因素COX回归分析患者的年龄、性别、血清AFP值、肿瘤大小、HBs Ag表达情况、复发状态和COTE 1表达水平对患者术后总生存时间的影响,在单因素分析中发现患者的血清AFP值相对危险度(Relative risk,RR)为5.292,P<0.05、复发状态相对危险度为4.461,P<0.05和COTE 1的表达水平相对危险度为21.087,P<0.05均为肝癌患者预后相关因素。在多因素COX比例风险回归分析显示,COTE 1表达水平可作为HCC病人独立的预后相关因素(相对危险度为12.34;P<0.05)。(4)Kaplan-Meier生存分析提示,COTE 1高表达患者的术后总生存期相对于COTE 1低表达者显著缩短(P<0.05)。结论(1)COTE 1在肝细胞癌组织中高表达,可能在肝细胞癌的发生及发展中发挥作用。(2)COTE 1高表达组预后较低表达组差,高AFP组患者预后较AFP低组差(3)COTE 1结合AFP可能是更好的判断患者预后的综合指标。更多还原

【Abstract】 ObjectiveExplore the recombinant human sequence similarity family 189,member B(Family with sequence similarity 189,member B,FAM189B),also known as the expression of COTE 1 in hepatocellular carcinoma and its relationship with the prognosis of hepatocellular carcinoma patients.Provide reference basis for clinical treatment and prevention.MethodsIn this retrospective research experiment,59 patients with primary hepatocellular carcinoma who underwent surgical treatment in the General Surgery of the Affiliated Hospital of Jiangsu University from January 2009 to January 2014 were included,and their liver cancer tissues and corresponding cancers were collected.Tissues(according to the tumor margin 2cm or more),using QRT-PCR method and Western blot method to detect the expression of COTE 1 m RNA in cancer tissues and adjacent non-hepatocellular carcinoma tissues,while using immunohistochemistry to detect the expression of COTE 1 protein in 59 liver cancer patients and adjacent non-hepatoma tissues Expression,divide it into low expression group and high expression group,and collect complete clinicopathological data(age,gender,serum AFP value,tumor size,HBs Ag expression)and postoperative follow-up information(total survival time and Recurrence),to analyze the relationship between the expression level of COTE 1and clinical pathological parameters and patient prognosis.Results(1)Immunohistochemical method was used to detect the expression of COTE 1 protein in 59 liver cancer patients’ cancer tissues and adjacent non-hepatocellular carcinoma tissues.Among them,37 cases of cancer tissues had high expression of COTE 1,accounting for 62.7%,and 24 cases of adjacent tissue had high expression of COTE 1.The expression of COTE 1 in tissues was higher than that in adjacent tissues(P = 0.017 <0.05).QRT-PCR and Western blot were used to detect the expression level of COTE 1 in cancer tissues and adjacent non-hepatoma tissues of 59 patients with liver cancer.The results showed that the expression of COTE 1 m RNA and protein in liver cancer tissues was higher than that in adjacent non-hepatoma tissues(P <0.01).(2)There was no correlation between age group and COTE 1(r = 0.081,P= 0.542);COTE 1 had a positive correlation with AFP expression(r = 0.706,P<0.001);COTE 1 had no correlation with tumor size(R = 0.205,P <0.119).According to the immunohistochemical score,patients with hepatocellular carcinoma were divided into a COTE 1 high expression group(> 4 points)and a COTE 1 low expression group(0 to 4 points).There was no statistically significant difference in immunohistochemical scores between different genders(Z =-1.002,P = 0.320);there was no statistical difference between HBs Ag positive and negative groups(Z =-0.514,P = 0.607);Immunohistochemical scores between tumor recurrence and non-recurrence groups were statistically different(Z =-2.425,P =0.042).(3)Univariate and multivariate COX regression analysis was used The influence of age,gender,serum AFP value,tumor size,HBs Ag expression,recurrence status and COTE 1 expression level on the patient’s overall survival time after surgery.The relative risk of serum AFP value was found in a single factor analysis(Relative risk,RR)Is 5.292,P <0.05,the relative risk of recurrence is 4.461,the relative risk of P <0.05 and the expression level of COTE1 is 21.087,and P <0.05 are all prognostic factors in patients with liver cancer.Multivariate COX proportional hazards regression analysis showed that COTE 1 expression level can be used as an independent prognostic factor in patients with HCC(relative risk12.34;P <0.05).(4)Kaplan-Meier survival analysis indicated that the overall postoperative survival time of patients with high expression of COTE 1 was significantly shorter than that of patients with low expression of COTE 1(P <0.05).Conclusion(1)COTE 1 is highly expressed in hepatocellular carcinoma and may play a role in the occurrence and development of hepatocellular carcinoma.(2)The prognosis of COTE 1 high expression is lower than that of the lower expression group,and the prognosis of patients in the high AFP group is worse than that of the low AFP group.(3)COTE 1 combined with AFP may be a better comprehensive indicator to judge the prognosis of patients.更多还原