【摘要】 目的研究肝细胞癌(hepatocellular carcinoma, HCC)患者血清可溶性MICA(soluble MHC class-Ⅰchain related gene A,sMICA)水平及MICA等位基因多态性与HCC分化程度的关系,为HCC的预防和治疗提供新的思路。方法按照Edmondson-Steiner四级(Ⅰ-Ⅳ)分级法将113例HCC患者分为高分化(Ⅰ-Ⅱ级)组(n=74)和低分化(Ⅲ-Ⅳ级)组(n=39),同时招募80例无亲缘关系的健康志愿者作为正常对照。收集对照组和HCC患者的外周血,通过酶联免疫吸附法(ELISA)检测各组血清sMICA水平,采用聚合酶链反应-直接测序法(PCR-SBT)对各组MICA等位基因进行测序分型。结果 HCC组血清ALT、AST、AFP、sMICA的浓度高于对照组(P<0.001)。HCC低分化组的血清sMICA浓度高于HCC高分化组(P=0.007),HCC高分化组和低分化组的血清ALT、AST、AFP浓度差异无统计学意义(P>0.05)。MICA-A4在HCC组的频率(11.5%)明显低于对照组(23.1%)(Pc=0.01),而MICA-A5在HCC组的频率(48.2%)则高于对照组(34.4%)(Pc=0.03),但MICA-A4、MICA-A5在HCC高分化组与低分化组的分布频率无明显差异(Pc值分别为0.67、0.31)。MICA*010在HCC组的频率(36.7%)明显高于对照组(15.6%)(Pc<0.001),而MICA*045在HCC组的频率(3.1%)低于对照组(13.1%)(Pc<0.001),但MICA*010、MICA*045在HCC高分化组与低分化组的分布频率差异无统计学意义(Pc值分别为0.28、0.42)。结论血清sMICA水平可作为HCC恶性程度的一种重要标志,MICA-A5和MICA*010可能是HCC的一个易感因素,MICA-A4和MICA*045可能是HCC的一个保护因素。更多还原

【Abstract】 Objective To explore the correlation between the MICA(MHC class-Ⅰ chain related gene A) polymorphisms, the amount of soluble MICA(sMICA) in the serum and the degree of hepatocellular carcinoma(HCC) differentiation, providing a novel idea for prevention and treatment of HCC. Methods The Edmondson-Steiner grade(Ⅰ-Ⅳ) was used to classify 113 HCC patients into two groups: well differentiated(grade Ⅰ-Ⅱ,n=74) and poorly differentiated(grade Ⅲ-Ⅳ,n=39). 80 unrelated healthy volunteers were recruited as the control group. The peripheral blood of HCC groups and the control group were collected. The concentration of serum sMICA was detected by enzyme-linked immunosorbent assay(ELISA) and the polymorphism of MICA was genotyped by polymerase chain reaction-direct sequencing(PCR-SBT). Results The concentration of ALT、AST、AFP、serum sMICA in the HCC groups was higher than that in the control group(P<0.001). The concentration of sMICA in the HCC poorly differentiated group was higher than that in the HCC well differentiated group(P=0.007). There was no significant difference in the levels of ALT, AST, and AFP between the HCC well differentiated group and HCC poorly differentiated group(P>0.05). The frequency of MICA-A4 in the HCC groups(11.5%) was significantly lower than that in the control group(23.1%,Pc=0.01), while the frequency of MICA-A5 in the HCC group(48.2%) was higher than that in the control group(34.4%,Pc=0.03). However, micA-A4 and MICA-A5 showed no significant difference in the distribution frequency between the HCC well differentiated group and the HCC poorly differentiated group(Pc value was 0.67 and 0.31, respectively). The frequency of MICA*010 in HCC groups(36.7%) was significantly higher than that in the control group(15.6%; Pc<0.001), while the frequency of MICA*045 in HCC group(3.1%) was lower than that in control group(13.1%;Pc<0.001). However, there was no significant difference in the distribution frequency of MICA*010 and MICA*045 in the well differentiated and poorly differentiated HCC groups(Pc value was 0.28 and 0.42, respectively). Conclusion The level of serum sMICA could be used as an important biomarker of HCC malignancy. The MICA-A5 and MICA*010 may be a susceptibility locus for HCC and MICA-A4 and MICA*045 allele may be a protective locus.更多还原