肝癌HLA-E基因的表达及对判断肝癌肝移植疗效的意义

Implication of human leukocyte antigen-E （HLA-E） expression in prognosis of patients with hepatocellular carcinoma undergoing liver transplantation

目的 观察肝癌患者人类白细胞抗原-E（HLA-E）及相关抗原的表达,以及其对判断肝癌肝移植预后的可行性和价值.方法 回顾性研究40例肝癌肝移植患者,检测HLA-ABC、HLA-E、抗原提呈辅助分子（β2-M、TAP）抗原在其原发灶和癌旁硬化组织中的表达,逆转录PCR法检测石蜡标本中HLA-E mRNA的表达,并将各抗原表达情况与肝移植的预后进行统计学分析.结果 与癌旁组织相比,癌巢HLA-ABC表达增强12例（30%）,一致21例（52.5%）,相对下调7例（17.5%）.HLA-E抗原在癌旁组织中表达不明显,癌巢阳性表达（＋＋/＋）为29例（72.5%）,P＜0.01,肝癌标本可检测出HLA-E mRNA的表达.β2-M和TAP在癌巢和癌旁组织中均有相同程度的表达,无统计学意义.随访期内HLA-E（＋＋/＋）患者移植后无瘤生存期较短（P＜0.05）.结论 肝癌HLA-E异常表达影响肝癌肝移植的疗效,提示其在肝癌免疫逃避中的重要作用.

Objective To investigate the expression of human leukocyte antigen - E （ HLA -E） and relative molecules in patients with human hepatocellular carcinoma （HCC）, and discuss their feasibility to judge patients＇prognosis after liver transplantation. Methods Forty cases of HCC undergo- ing liver transplantation were retrospectively analyzed. The expression of HLA - ABC, HLA - E, and anti- gen presenting auxiliary molecules （ [32 - M ,TAP） was detected in paraffin - embedded primary HCC and adjacent cirrhotic tissues by immunohistochemistry. The expression of HLA - E mRNA was assayed by re- verse transcriptase - PCR in paraffin - embedded samples. The relationship between the expression and prognosis following liver transplantation was statistically analyzed. Results Compared with paracancer- ous tissues,the HLA -ABC expression in tumor tissues was increased in 12 cases （30%） ,identical in 21 cases （52.5%）,and reduced in 7 cases （12.5%） respectively. HLA- E antigen was expressed weakly in paracancerous tissues, but strongly in tumor tissues of 29 cases （ 72.5 %, P 〈 0.01 ）. The HLA - E mRNA in paraffin - embedded tumor tissues was detected by RT - PCR with high sensitivity. [32 - M and TAP were expressed in HCC or paracancerous tissues to varying degrees. During the follow - up period, the tumor - free survival in patients with high HLA - E expression （ ＋ / ＋ ＋ ） in tumor tissues was shorter after liver transplantation （ P 〈 0.05 ）. Conclusion The over - expression of HLA - E reduces the therapeutic efficacy of liver transplantation to HCC, suggesting its important roles in immune escape of HCC.