肝癌患者血浆循环DNA杂合性缺失的检测及其临床意义

目的检测HCC患者血浆循环DNA杂合性缺失（LOH），并探讨将其作为有关临床预测标记的可能性。方法选择位于染色体8p上3个具有高度多态性的微卫星标记D8S277、D8S298和D8S1771，对62份HCC患者血浆循环DNA进行LOH检测，并进一步探讨LOH与患者HBsAg表达、是否肝硬化、血清AFP水平、肿瘤大小及细胞分化程度和有无肝内转移等临床病理特征之间的关系。结果在62份HCC患者血浆循环DNA标本中，36份（58．1％）在1个或多个位点发生LOH，D8S277、D8S298和D8S1771位点杂合度分别为74．2％（46／62）、75．8％（47／62）和69．4％（43／62），LOH频率分别为32．6％（15／46）、44．7％（21／47）和46．5％（20／43）。D8S298位点有肝内转移患者血浆循环DNA标本的LOH频率（62．5％）明显高于无肝内转移者（26．1％），差异有统计学意义（P〈0．05）；其他临床病理特征与3个位点上的LOH频率无明显相关。结论血浆循环DNA中D8S298位点LOH有可能成为HCC术后转移复发及预后的一个潜在的预测标记。

Loss of heterozygosity of plasma circulating DNA from hepatocellular carcinoma patients and its clinical significance

OBJECTIVES: To detect the loss of heterozygosity (LOH) of circulating DNA in the plasma of patients with hepatocellular carcinoma (HCC), and to assess its potential as a clinical predictive marker. METHODS: Three high-polymorphic microsatellite markers D8S277, D8S298 and D8S1771 located at chromosome 8p were selected to detect LOH in plasma DNA of 62 HCC patients. The associations between LOH and its clinicopathological features, including HBsAg, liver cirrhosis, serum AFP level, tumor size, tumor cell differentiation, and intrahepatic metastasis were also examined. RESULTS: In plasma DNA of the 62 HCC patients, LOH was found at one or several loci in 36 (58.1%), and heterozygosity at D8S277, D8S298, and D8S1771 loci was 74.2% (46/62), 75.8% (47/62), and 69.4% (43/62), respectively. LOH frequency at D8S277, D8S298 and D8S1771 was 32.6% (15/46), 44.7% (21/47), and 46.5% (20/43), respectively. LOH in plasma DNA was more frequently detected in the patients with intrahepatic cancer metastasis than those without metastasis (62.5 percent vs. 26.1 percent, P < 0.05); however, no statistically significant correlations were observed between LOH at these loci and other clinicopathological features analyzed in this study. CONCLUSIONS: LOH at D8S298 in plasma DNA may be a potential predictive marker of intrahepatic metastatic recurrence after surgical resection of the HCC.