中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (9): 656-660.doi: 10.19401/j.cnki.1007-3639.2020.09.003

• 论著 • 上一篇    下一篇

膜辅助蛋白CD46 rs1970530遗传变异对肝癌发病风险的影响

徐珊珊 1 ,宋琴琴 1 ,仵红娇 2 ,付 宁 2 ,车玲玉 2 ,金 敏 1 ,刘 冲 1 ,韩素桂 3 ,张雪梅 2 ,张 志 1   

  1. 1. 华北理工大学附属唐山市工人医院肿瘤科,河北 唐山 063000 ;
    2. 华北理工大学生命科学学院,河北 唐山 063210 ;
    3. 华北理工大学附属唐山市人民医院核医学检验科,河北 唐山 063000
  • 出版日期:2020-09-30 发布日期:2020-10-10
  • 通信作者: 张 志 E-mail: zhi1969@163.com
  • 基金资助:
    国家自然科学基金(81101483);河北省自然科学基金重点项目(H2017209233);唐山市科技创新团队培养计划(14130225B)。

Genetic variation in membrane cofactor protein CD46 rs1970530 affects the risk of hepatocellular carcinoma

XU Shanshan 1 , SONG Qinqin 1 , WU Hongjiao 2 , FU Ning 2 , CHE Lingyu 2 , JIN Min 1 , LIU Chong 1 , HAN Sugui 3 , ZHANG Xuemei 2 , ZHANG Zhi 1   

  1. 1. Department of Oncology, Tangshan Gongren Hospital, North China University of Science and Technology, Tangshan 063000, Hebei Province, China; 2. College of Life Sciences, North China University of Science and Technology, Tangshan 063210, Hebei Province, China; 3. Nuclear Medicine Laboratory, Tangshan People’s Hospital, North China University of Science and Technology, Tangshan 063000, Hebei Province, China
  • Online:2020-09-30 Published:2020-10-10
  • Contact: ZHANG Zhi E-mail: zhi1969@163.com
  • Supported by:

摘要: 背景与目的:膜辅助蛋白CD46可保护宿主细胞免受补体依赖的细胞毒性作用,研究表明,CD46可能作为肝细胞癌(hepatocellular carcinoma,HCC)患者的潜在生物标志物。探讨CD46基因表达及启动子区遗传变异与HCC发病风险的关系。方法:通过基因表达谱交互分析(gene expression profiling interactive analysis,GEPIA)在线网站分析HCC组织和正常肝组织CD46表达的差异;2011—2015年在华北理工大学附属唐山市工人医院和华北理工大学附属唐山市人民医院经病理学检查确诊且未经放化疗的240例HCC患者作为病例组,对照组为同时期入院体检的500名健康人群。采用聚合酶链反应-限制性片段长度多态性分析(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)法进行基因分型,检测两组基因型频率和等位基因频率,评估CD46 rs1970530遗传变异与HCC发病风险的关系。结果:CD46在HCC组织与正常组织中的表达差异有统计学意义(P<0.05)。经非条件logistic回归分析发现,CD46 rs1970530至少携带一个G等位基因型在病例组及对照组之间差异有统计学意义(OR=0.666,95% CI:0.448~0.990,P<0.05);两组间等位基因G频率差异有统计学意义(OR=0.689,95% CI:0.478~0.994,P<0.05)。分层分析结果显示,至少携带一个G等位基因者可降低高年龄组(>60岁)(P=0.048)和男性(P=0.023)人群的HCC发病风险,在女性和低年龄组(≤60岁)中差异无统计学意义(P>0.05)。按吸烟状态进行分层分析,rs1970530变异与HCC易感性无明显关联(P>0.05)。结论:HCC中CD46基因高表达及CD46 rs1970530遗传变异影响HCC发病风险。

关键词: 膜辅助蛋白CD46, 肝细胞癌, 单核苷酸多态性, 易感性

Abstract: Background and purpose: Membrane cofactor protein CD46 protects host cells from complement-dependent cytotoxicity and may be a potential molecular marker for hepatocellular carcinoma (HCC). This study aimed to investigate the correlation between the gene expression of CD46 with the genetic variation of CD46 promoter and the risk of HCC. Methods: The difference in CD46 expression between HCC tissues and normal liver tissues was analyzed by gene expression profiling interactive analysis (GEPIA) online website. From 2011 to 2015, 240 HCC patients were confirmed by pathological diagnosis in Tangshan Gongren Hospital, North China University of Science and Technology and Tangshan People’s Hospital, North China University of Science and Technology, and 500 healthy people enrolled as the control group in the same period. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect genotype frequencies and allele frequencies between two groups. The relationship between the genetic variation of CD46 rs1970530 and the risk of HCC was evaluated. Results: The expression of CD46 was significantly different between HCC tissues and normal tissues (P<0.05). Unconditional logistic regression analysis indicated the difference in CD46 rs1970530 genotype carrying at least one G allele was statistically significant between the case group and the control group (OR=0.666, 95% CI: 0.448-0.990, P<0.05), and there was also a significant difference in the frequency of the allele G (OR=0.689, 95% CI: 0.478-0.994, P<0.05). The stratification analysis showed that CD46 rs1970530 genotype carrying at least one G allele could reduce the risk of HCC in the advanced age group (>60 years) (P=0.048) and men (P=0.023), however, there was no difference in women and younger age groups between the HCC and the healthy control (≤60 years) (P>0.05). Smoking stratification analysis indicated that there was no significant correlation between rs1970530 mutation and HCC susceptibility (P>0.05). Conclusion: The high gene expression of CD46 in HCC and the genetic variation of CD46 rs1970530 affect the risk of HCC.

Key words: Membrane cofactor protein CD46, Hepatocellular carcinoma, Single nucleotide polymorphism, Susceptibility