Yang Xin-Rong, Xu Yang, Shi Guo-Ming, Fan Jia, Zhou Jian, Ji Yuan, Sun Hui-Chuan, Qiu Shuang-Jian, Yu Bing, Gao Qiang, He Yi-Zhou, Qin Weng-Zhen, Chen Rong-Xin, Yang Guo-Huan, Wu Bing, Lu Qing, Wu Zhi-Quan, Tang Zhao-You
Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai Cancer Institute, Shanghai, PR China.
Clin Cancer Res. 2008 Jun 15;14(12):3850-9. doi: 10.1158/1078-0432.CCR-07-4338.
Cytokeratin 10 (CK10) was found to be expressed differently in human hepatocellular carcinoma (HCC) cell lines with different metastatic potentials in our previous research. The aim of this study was to assess the value of CK10 alone or in combination with cytokeratin 19 (CK19) in predicting tumor recurrence after curative resection in HCC patients.
CK10 expression in stepwise metastatic HCC cell lines and tumor tissues from 50 HCC patients was investigated using immunofluorescence assay, quantitative real-time reverse transcription-PCR, and Western blot analyses. Tumor tissue microarrays of 300 HCC patients who underwent curative resection between 1997 and 2000 were used to detect the expressions of CK10 and CK19. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests.
CK10 was overexpressed in the high metastatic HCC cell line and in tumor tissues of recurrent patients. Both univariate and multivariate analyses revealed that CK10 was a significant predictor for overall survival (OS) and disease-free survival, and that CK19 was a significant predictor for OS. CK10 expression was correlated with poor prognosis regardless of alpha-fetoprotein, tumor-node-metastasis stage, and vascular invasion. The 7-year OS and disease-free survival rates in CK10+ and/or CK19+ patients were 30.0% and 37.6%, respectively, which were significantly lower than that of CK10-/CK19- patients (56.1% and 60.0%, respectively; P < 0.001).
CK10 is associated with HCC invasiveness. CK10 alone, or in combination with CK19, can be a novel predictor for poor prognosis of HCC patients after curative resection.
在我们之前的研究中发现,细胞角蛋白10(CK10)在具有不同转移潜能的人肝癌(HCC)细胞系中表达不同。本研究的目的是评估单独的CK10或与细胞角蛋白19(CK19)联合使用在预测HCC患者根治性切除术后肿瘤复发中的价值。
使用免疫荧光分析、定量实时逆转录 - PCR和蛋白质印迹分析,研究了逐步转移的HCC细胞系和50例HCC患者肿瘤组织中CK10的表达。使用1997年至2000年间接受根治性切除的300例HCC患者的肿瘤组织微阵列来检测CK10和CK19的表达。评估了这些患者的临床病理数据。使用Kaplan - Meier生存估计和对数秩检验评估预后意义。
CK10在高转移HCC细胞系和复发患者的肿瘤组织中过表达。单变量和多变量分析均显示,CK10是总生存期(OS)和无病生存期的重要预测指标,CK19是OS的重要预测指标。无论甲胎蛋白、肿瘤 - 淋巴结 - 转移分期和血管侵犯情况如何,CK10表达均与预后不良相关。CK10 +和/或CK19 +患者的7年OS率和无病生存率分别为30.0%和37.6%,显著低于CK10 - /CK19 -患者(分别为56.1%和60.0%;P < 0.001)。
CK10与HCC侵袭性相关。单独的CK10或与CK19联合使用,可以作为HCC患者根治性切除术后预后不良的新预测指标。