Cheung Siu Tim, Leung Ka Ling, Ip Ying Chi, Chen Xin, Fong Daniel Y, Ng Irene O, Fan Sheung Tat, So Samuel
Department of Surgery, Centre for the Study of Liver Disease, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong, China.
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):551-6.
Hepatocellular carcinoma (HCC) patients with the same clinicopathologic features can have remarkably different disease outcomes after curative hepatectomy. To address this issue, we evaluated the cDNA microarray gene expression profiles of HCCs and identified claudin-10 expression level was associated with disease recurrence. The aim of the current study is to validate the microarray data by an alternative research method applicable for routine practice.
Quantitative reverse transcription-PCR (RT-PCR) was used to validate the microarray data on claudin-10 expression level. The assay was repeated on a separate HCC sample set to consolidate the prognostic significance of claudin-10.
Claudin-10 expression level by quantitative RT-PCR and by microarray measurement showed a high concordance (r = 0.602, P < 0.001). Quantitative RT-PCR was repeated on a separate HCC sample set and the association of claudin-10 expression with recurrence was again confirmed (hazard ratio, 1.2; 95% confidence interval, 1.0-1.4; P = 0.011). By multivariable Cox regression analysis, claudin-10 expression and pathologic tumor-node-metastasis stage were independent factors for prediction of disease recurrence.
Claudin-10 expression of HCC can be used as a molecular marker for disease recurrence after curative hepatectomy.
具有相同临床病理特征的肝细胞癌(HCC)患者在接受根治性肝切除术后,疾病转归可能显著不同。为解决这一问题,我们评估了HCC的cDNA微阵列基因表达谱,并确定紧密连接蛋白10(Claudin-10)表达水平与疾病复发相关。本研究的目的是通过一种适用于常规实践的替代研究方法来验证微阵列数据。
采用定量逆转录聚合酶链反应(RT-PCR)来验证关于Claudin-10表达水平的微阵列数据。在另一组HCC样本上重复该检测,以强化Claudin-10的预后意义。
定量RT-PCR和微阵列测量所得的Claudin-10表达水平显示出高度一致性(r = 0.602,P < 0.001)。在另一组HCC样本上重复定量RT-PCR,再次证实了Claudin-10表达与复发之间的关联(风险比,1.2;95%置信区间,1.0 - 1.4;P = 0.011)。通过多变量Cox回归分析,Claudin-10表达和病理肿瘤-淋巴结-转移分期是预测疾病复发的独立因素。
HCC的Claudin-10表达可作为根治性肝切除术后疾病复发的分子标志物。