Loss of heterozygosity at D8S298 is a predictor for long-term survival of patients with tumor-node-metastasis stage I of hepatocellular carcinoma
Loss of heterozygosity at D8S298 is a predictor for long-term survival of patients with tumor-node-metastasis stage I of hepatocellular carcinoma
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DOI：
10.1158/1078-0432.ccr-07-0593
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发表时间：
2007-12-15
影响因子：
11.5
通讯作者：
Tang, Zhao-You
中科院分区：
文献类型：
--
作者：
Pang, Jin-Zhong;Qin, Lun-Xiu;Tang, Zhao-You
目的：我们前期的研究表明染色体8p缺失与肝细胞癌（HCC）的转移有关。本研究旨在确定8p缺失是否可以用于预测HCC患者的预后，特别是早期HCC患者的预后。实验设计：本研究共纳入131例行根治性肝切除术的TNM期HCC患者。采用8p染色体上的10个微卫星标记，以及1p、17p、4q、13q和16q染色体上的14个微卫星标记检测杂合性缺失（LOH），并分析其与患者5年总生存期（OS）和无病生存期（DFS）的相关性。结果：在整个队列患者中，这24个位点的平均LOH频率为43.2%；D8S298和D1S199的LOH频率分别为31.5%和33.7%。在TNM期HCC患者中，D8S298的LOH与较差的5年OS （P = 0.008）和DFS （P = 0.038）相关。同样，与D1S199时无LOH的患者相比，D1S199时LOH患者的5年OS （P < 0.001）和DFS （P = 0.014）更差。在多变量分析中，D8S298的LOH是DFS降低的独立预测因子（风险比0.372,95% 95%可信区间0.146-0.948,P = 0.038），而D1S199的LOH是OS降低的独立预测因子（风险比0.281,95%可信区间0.123-0.643,P = 0.003）。结论：D8S298和D1S199的LOH与TNM期HCC患者治愈性切除后较差的生存率独立相关，可以作为该亚组患者的新的预后预测指标。
Purpose: Our previous studies have shown that chromosome 8p deletion correlates with metastasis of hepatocellular carcinoma (HCC). This study was to determine whether 8p deletion could be used in predicting the prognosis of patients with HCC, particularly in those with early stage of HCC.Experimental Design: A total of 131 patients with tumor-node-metastasis (TNM) stage I of HCC who underwent curative liver resection were enrolled. Loss of heterozygosity (LOH) was examined using 10 microsatellite markers at chromosome 8p, as well as 14 microsatellites at chromosome 1p, 17p, 4q, 13q, and 16q, and their association with 5-year overall survival (OS) and disease-free survival (DFS) of patients was analyzed.Results: In the entire cohort of patients, the mean LOH frequency at these 24 loci was 43.2%; LOH frequencies at D8S298 and D1S199 were 31.5% and 33.7%, respectively. LOH at D8S298 was associated with a worse 5-year OS (P = 0.008) and DFS (P = 0.038) in patients with TNM stage I of HCC. Likewise, the patients with LOH at D1S199 had a worse 5-year OS (P < 0.001) and DFS (P = 0.014) compared with those without LOH at D1S199. In multivariate analyses, LOH at D8S298 was an independent predictor of decreased DFS (hazard ratio, 0.372; 95% 95% confidence interval, 0.146-0.948; P = 0.038), whereas LOH at D1S199 was an independent predictor of decreased OS (hazard ratio, 0.281; 95% confidence interval, 0.123-0.643; P = 0.003).Conclusions: LOH at D8S298 and D1S199 is independently associated with a worse survival in patients with TNM stage I of HCC after curative resection and could serve as novel prognostic predictors for this subgroup of patients.