文章摘要
原发性肝细胞癌患者 p53基因突变的特征和临床意义的研究
Characteristic and clinical implication of p53 gene mutation in the patients with primary hepatocellula
  
DOI:10.3969/j.issn.1007-8134.2022.05.009
中文关键词: 慢性乙型肝炎肝硬化  原发性肝细胞癌  p53基因  甲胎蛋白异质体  高尔基糖蛋白-73  异常凝血酶原  临床特征  预后
英文关键词: chronic hepatitis B cirrhosis  primary hepatocellular carcinoma  p53 gene  alpha-fetoprotein L3  golgi protein-73  des-γ-carboxy-prothrombin  clinical characteristic  prognosis
基金项目:秦皇岛市市级科学技术研究与发展计划自筹经费项目(202101A139)
作者单位
李艳婷 秦皇岛市第三医院检验科 
杨?志 秦皇岛市第三医院检验科 
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中文摘要:
      [摘要] 目的  探讨p53基因突变在原发性肝细胞癌(hepatocellular carcinoma, HCC)患者中的特征和临床意义,并分析其对预后的影响。方法 选取我院2019年1月1日—2020年4月30日收治的慢性乙型肝炎肝硬化和HCC患者各120例,分别作为慢性乙型肝炎肝硬化组和HCC组。选取同期于我院行体检的120例健康体检者作为健康对照组。采用化学发光法检测HCC患者血清特异性肿瘤标志物甲胎蛋白异质体(alpha-fetoprotein L3, AFP-L3)、高尔基糖蛋白-73(golgi protein 73, GP73)、异常凝血酶原(des-γ-carboxy-prothrombin, DCP)水平。采用聚合酶链反应-限制性片段长度多态性方法检测3组p53第4外显子72位密码子(p53 Arg72Pro)基因型,分析不同组间p53 Arg72Pro基因型差异,并比较HCC组患者不同p53 Arg72Pro基因型间AFP-L3、GP73、DCP水平及HBV DNA阳性率和生存率差异。结果 HCC组携带Pro/Pro基因型患者比例为33.3%,高于慢性乙型肝炎肝硬化组的14.2%和健康对照组的13.3%,差异均具有统计学意义(P均<0.05)。在HCC患者中,Pro/Pro型患者发病年龄明显小于Arg/Pro型和Arg/Arg型患者,而巴塞罗那分期为C/D期和伴有淋巴结转移的患者比例明显高于Arg/Pro型和Arg/Arg型患者, HBV DNA检测阳性率明显高于Arg/Arg型,血清特异性肿瘤标志物AFP-L3、GP73、DCP水平均明显高于Arg/Arg型和Arg/Pro型患者,差异均具有统计学意义(P均<0.05)。Arg/Arg型HCC患者生存率为83.3%,高于Arg/Pro型和Pro/Pro型患者的63.3%,差异具有统计学意义(P<0.05)。结论 p53 Arg72Pro基因突变与HCC的发生存在密切关联,且与多个HCC血清特异性肿瘤标志物密切相关,可能是加速患者癌变进展过程中的关键调节因子。
英文摘要:
      [Abstract] Objective?To investigate the relationship between the characteristics and clinical implication of p53 gene mutations in patients with primary hepatocellular carcinoma (HCC) and its impact on prognosis. Methods?A total of 120 patients with chronic hepatitis B cirrhosis and HCC admitted to our hospital from January 1, 2019 to April 30, 2020 were enrolled as chronic hepatitis B cirrhosis group and HCC group, respectively. At the same time, 120 healthy people in our hospital physical examination were enrolled as the healthy control group. Chemiluminescence method was used to detect serum specific tumor markers alpha-fetoprotein L3 (AFP-L3) , golgi protein 73 (GP73), des-γ-carboxy-prothrombin (DCP) levels. The genotypes of p53 Arg72Pro at codon 72 of exon 4 (p53 Arg72Pro) were detected by polymerase chain react-restriction fragment length polymorphism, and the differences of p53 Arg72Pro genotypes among different groups were analyzed. The levels of AFP-L3, GP73, DCP, HBV DNA positive rate and survival rate were compared between different p53 Arg72Pro genotypes in HCC group. Results The proportion of patients carrying Pro/Pro genotype in HCC group was 33.3%, which was higher than that in chronic hepatitis B cirrhosis group (14.2%) and healthy control group (13.3%), and the differences were statistically significant (P<0.05). Among HCC patients, the age of HCC in Pro/Pro patients was significantly younger than that in Arg/Pro and Arg/Arg patients, while the proportion of patients with BCLC stage C/D and lymph node metastasis was significantly higher than that in Arg/Pro and Arg/Arg patients. The positive rate of HBV DNA detection was significantly higher than that of Arg/Arg type, and the serum levels of specific tumor markers AFP-L3, GP73 and DCP were significantly higher than those of Arg/Arg type and Arg/Pro type patients, the difference were statistically significant (P<0.05). The survival rate of patients with Arg/Arg type HCC was 83.3%%, which was higher than that of patients with Arg/Pro type and Pro/Pro type, and the difference was statistically significant (P<0.05). Conclusions?P53 Arg72Pro gene mutation is closely associated with the occurrence of HCC, and is closely related to several HCC serum-specific tumor markers, which may be a key regulator in accelerating the progression of cancer.
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