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目的探讨细胞周期信号通路相关基因CDC25C、CDKN2A(p16)、MCM4、MCM7、PARDC(DNA-PK)、RAD21、RBL2(p107)、YWHAB(14-3-3)、SMAD3、KAT2B、CHEK1单核苷酸多态性(SNP)与肝细胞癌(HCC)临床病理特征的关系,为HCC的预后预测提供科学依据。方法于2007年7月—2011年3月整群抽取在广西医科大学第一附属医院肝胆外科就诊和治疗的498例新发HCC患者进行相关流行病学调查和临床病理资料的收集,并采集其空腹静脉血提取血液样本DNA,采用基质辅助激光解吸电离飞行时间质谱方法对14个细胞周期信号通路相关基因SNP位点进行基因分型。结果在校正了年龄、性别、民族、HCC家族史、HBs Ag、吸烟和饮酒情况后,多因素非条件logistic回归分析结果显示,携带YWHAB基因rs2425675位点等位基因A基因型AG/AA患者的包膜侵犯风险为基因型GG患者的2.097倍(OR=2.097,95%CI=1.034~4.256);携带RBL2基因rs3929位点等位基因C基因型GC/CC患者的包膜侵犯风险为基因型GG患者的2.234倍(OR=2.234,95%CI=1.100~4.534);携带CDC25C基因rs3734166位点等位基因G基因型GA/GG患者的子灶发生风险为基因型AA患者的0.460倍(OR=0.460,95%CI=0.259~0.816),癌栓发生风险为基因型AA患者的0.651倍(OR=0.651,95%CI=0.439~0.965);携带CHEK1基因rs515255位点等位基因T基因型TC/TT患者的子灶发生风险为基因型CC患者的0.451倍(OR=0.451,95%CI=0.252~0.807),肿瘤数目多发的风险为基因型CC患者的0.655倍(OR=0.655,95%CI=0.442~0.971)。分层分析结果显示,YWHAB基因rs2425675位点在无HCC家族史、不吸烟、不饮酒的患者中,其SNP多态性与肝癌肿瘤包膜侵犯和假包膜的发生存在统计学关联(均P<0.05);CDC25C基因rs3734166位点在无HCC家族史、不吸烟、不饮酒、HBs Ag阴性和阳性的患者中,其SNP多态性与子灶、癌栓、脉管侵犯和肝硬化的发生存在统计学关联(均P<0.05);CHEK1基因rs515255位点在无HCC家族史、不吸烟、饮酒、不饮酒和HBs Ag阳性的患者中,其SNP多态性与包膜侵犯、子灶的发生和肿瘤数目多发存在统计学关联(均P<0.05);RBL2基因rs3929位点在吸烟、不吸烟、饮酒、不饮酒和HBs Ag阴性患者中,其SNP多态性与包膜侵犯和脉管侵犯的发生存在统计学关联(均P<0.05)。结论 YWHAB、RBL2、CDC25C和CHEK1基因SNP多态性可能与HCC的临床病理特征相关。
Objective To investigate the expressions of CDC25C, CDKN2A (p16), MCM4, MCM7, PARDC (DNA-PK), RAD21, RBL2 (p107), YWHAB (14-3-3), SMAD3, KAT2B, CHEK1 mononuclear The relationship between acid polymorphism (SNP) and the clinicopathological features of hepatocellular carcinoma (HCC) provides a scientific basis for the prognosis prediction of HCC. Methods A total of 498 newly diagnosed HCC patients treated and treated in the Hepatobiliary Surgery Department of the First Affiliated Hospital of Guangxi Medical University from July 2007 to March 2011 were collected for epidemiological investigation and clinical pathological data collection and collection Fasting venous blood was used to extract DNA from blood samples. Genotypes of 14 SNPs in cell cycle signaling pathways were genotyped by matrix-assisted laser desorption / ionization time-of-flight mass spectrometry. Results After adjusting for age, gender, ethnicity, family history of HCC, HBs Ag, smoking and drinking, multivariate non-conditional logistic regression analysis showed that patients with AG genotype AA / rs2425675 carrying YWHAB gene The risk of invasion of envelope was 2.097-fold (OR = 2.097, 95% CI = 1.034-4.256) in patients with GG genotype. The risk of envelope invasion was GC / CC with rs3929 allele of RBL2 gene genotype (OR = 2.234, 95% CI = 1.100 ~ 4.534). The risk of the foci in GA / GG patients with G allele at rs3734166 locus of CDC25C gene was 0.460 times that in patients with AA genotype = 0.460, 95% CI = 0.259-0.816). The risk of cancer embolus was 0.651-fold (OR = 0.651, 95% CI = 0.439-0.965) in genotype AA patients. The T genotype of rs515255 allele carrying CHEK1 gene The risk of sub-tumor in TC / TT patients was 0.451-fold (OR = 0.451, 95% CI = 0.252-0.807) in patients with genotype CC and 0.655-fold (OR = 0.655, 95) in patients with genotype CC % CI = 0.442 ~ 0.971). Hierarchical analysis showed that rs2425675 locus of YWHAB gene in patients without family history of HCC, non-smoking, non-alcohol drinking, the SNP polymorphism and tumor envelope invasion of hepatocellular carcinoma and the occurrence of pseudocapsules were statistically significant (P <0.05). The rs3734166 locus of CDC25C gene was associated with the occurrence of sub-lesion, tumor thrombus, vascular invasion and cirrhosis in patients with no history of HCC, no smoking, no drinking, negative and positive HBsAg There was statistical significance (all P <0.05). In rs515255 locus of CHEK1 gene, there was no association between SNP polymorphism and envelopment in patients with no family history of HCC, alcohol consumption, alcohol consumption and non-alcohol drinking, (P <0.05). The polymorphism of rs3929 of RBL2 gene in smoking, non-smoking, drinking, non-alcoholic and HBsAg-negative patients was associated with the invasion of envelope and vascular The incidence of violations were statistically significant (all P <0.05). Conclusion The polymorphisms of YWHAB, RBL2, CDC25C and CHEK1 SNPs may be related to the clinicopathological features of HCC.