人白细胞DR抗原表达水平在预测肝癌患者预后中的作用

Role of human leukocyte antigen-DR expression on predicting the prognosis of hepatocellular carcinoma

目的 探讨人白细胞DR抗原（HLA-DR）在肝癌患者中的表达水平及其预测预后的临床价值。方法 选择2012年8月至2014年2月我院保存的97例原发性肝癌组织标本作为研究对象（病例组），并选择相应邻近正常肝脏组织作为对照组，采用免疫组织化学法检测两组标本组织中的HLA-DR表达水平，并分析其与临床病理特征、复发及预后的关系。结果 病例组标本组织中HLA-DR阳性表达率为55.67%，高于对照组的21.65%，差异有统计学意义（χ2=23.671，P〈0.001）。肿瘤直径≥4cm、Ⅲ～Ⅳ期、低分化、胆管细胞癌、未发生淋巴结转移的原发性肝癌病灶组织中HLA-DR阳性表达率高于肿瘤直径＜4cm、Ⅰ～Ⅱ期、中高分化、肝细胞癌、有淋巴结转移的原发性肝癌病灶组织，差异有统计学意义（χ2=10.481，P=0.001； χ2=18.854，P〈0.001； χ2=9.876，P=0.002； χ2=6.834，P=0.009； χ2=30.668，P〈0.001）。HLA-DR阴性患者2年、3年复发率为27.91%、46.51%，分别低于HLA-DR阳性患者的50.00%、70.37%，差异均有统计学意义（χ2=4.860，P=0.028； χ2=5.668，P=0.017）。HLA-DR阳性患者中位生存时间（33.64个月）短于HLA-DR阴性患者（36.88个月），差异有统计学意义（χ2=10.356，P＜0.001）。TNM分期为Ⅲ～Ⅳ期（OR=0.899，95%CI为0.721-0.995，P=0.012）、HLA-DR阳性（OR=1.125，95%CI为1.025-2.568，P=0.018）不利于肝癌患者预后。结论 HLA-DR在原发性肝癌组织中异常表达，可能参与了肝癌的发生、发展过程，并且其表达增高提示肝癌患者术后复发率高、生存时间短。

Objective To explore the expression of human leukocyte antigen DR （HLA-DR） in hepatocellular carcinoma and its clinical values in predicting prognosis. Methods The primary hepatocellular carcinoma tissues of 97 patients in our hospital from August 2012 to February 2014 were enrolled as subjects （case group）, and the adjacent normal liver tissues were selected as control （control group, n=97）. The expressions of HLA-DR in the two groups were detected by immunohistochemistry, and the relationships between HLA-DR expression and clinicopathological features, recurrence and prognosis were analyzed. Results The positive expression rate of HLA-DR in specimens of case group was 55.67%, which was higher than 21.65% in control group, and the difference was statistically significant （χ2=23.671, P〈0.001）. The positive expression rates of HLA-DR in tumor tissues with diameter ≥4cm, Ⅲ-Ⅳ stage, poorly differentiated, bile duct cell carcinoma, no lymph node metastasis were higher than those in tumor tissues with diameter 〈4cm, Ⅰ-Ⅱ stage, medium and well differentiated, hepatocellular carcinoma, lymph node metastasis respectively, and the differences were statistically significant （χ2=10.481, P=0.001; χ2=18.854, P〈0.001; χ2=9.876, P=0.002; χ2=6.834, P=0.009; χ2=30.668,P〈0.001）. The recurrence rates of 2 years and 3 years were 27.91% and 46.51% in patients with negative expression of HLA-DR respectively, which were lower than 50.00% and 70.37% in patients with positive expression of HLA-DR respectively, and the differences were statistically significant （χ2=4.860, P=0.028; χ2=5.668, P=0.017）. The median survival time of patients with HLA-DR positive expression was 33.64 months, which was shorter than 36.88 months in patients with negative expression, and the difference was statistically significant （χ2=10.356, P〈0.001）. TNM staging Ⅲ-Ⅳ （OR=0.899, 95%CI： 0.721-0.995, P=0.012） and positive expression of HLA-DR （OR=1.125, 95%CI： 1.025-2.568, P=0.018） were unfavorable to the prognosis of hepatocellular carcinoma patients. Conclusion HLA-DR expresses abnormally in patients with primary hepatocellular carcinoma, which may be involved in the occurrence and development of hepatocellular carcinoma, and the upregulation of HLA-DR in patients with hepatocellular carcinoma indicates a high recurrence rate and short survival time.