Pang Jin-Zhong, Qin Lun-Xiu, Ren Ning, Hei Zhen-Yu, Ye Qing-Hai, Jia Wei-Dong, Sun Bing-Sheng, Lin Guo-Ling, Liu Dao-Yong, Liu Yin-Kun, Tang Zhao-You
Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai, PR China.
Clin Cancer Res. 2007 Dec 15;13(24):7363-9. doi: 10.1158/1078-0432.CCR-07-0593.
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.
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.
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).
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.
我们之前的研究表明,8号染色体短臂缺失与肝细胞癌(HCC)转移相关。本研究旨在确定8号染色体短臂缺失是否可用于预测HCC患者的预后,尤其是早期HCC患者的预后。
共纳入131例行根治性肝切除术的肿瘤-淋巴结-转移(TNM)I期HCC患者。使用位于8号染色体短臂的10个微卫星标记以及位于1号染色体、17号染色体、4号染色体长臂、13号染色体和16号染色体的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(OS)和无病生存(DFS)的相关性。
在整个患者队列中,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%。D8S298位点的LOH与TNM I期HCC患者较差的5年OS(P = 0.008)和DFS(P = 0.038)相关。同样,与D1S199位点无LOH的患者相比,D1S199位点有LOH的患者5年OS较差(P < 0.001),DFS较差(P = 0.014)。在多变量分析中,D8S298位点的LOH是DFS降低的独立预测因素(风险比,0.372;95%置信区间,0.146 - 0.948;P = 0.038),而D1S199位点的LOH是OS降低的独立预测因素(风险比,0.281;95%置信区间,0.123 - 0.643;P = 0.003)。
D8S298和D1S199位点的LOH与根治性切除术后TNM I期HCC患者较差的生存率独立相关,并可作为该亚组患者新的预后预测指标。