Department of Cell Biology and Cell Engineering Research Center, State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Carcinogenesis. 2012 May;33(5):1040-5. doi: 10.1093/carcin/bgs098. Epub 2012 Feb 8.
Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence-activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE.
先前的研究报告称,外周血白细胞端粒长度可预测多种癌症的临床结局。然而,白细胞端粒长度是否与肝细胞癌(HCC)的预后相关仍有待确定。在这项研究中,我们使用基于实时 PCR 的方法测量了 269 名来自两家独立医院接受经动脉化疗栓塞(TACE)治疗的 HCC 患者外周血白细胞的相对端粒长度(RTL)。分析了 RTL 与 HCC 患者总体生存率(OS)之间的关系。评估了不同白细胞 RTL 的 HCC 患者的免疫功能。多变量分析表明,长白细胞 RTL 与 HCC 患者的不良 OS 显著相关,风险比为 2.04(95%置信区间,1.46-2.86;P < 0.001)。Kaplan-Meier 分析显示,长 RTL 和短 RTL 组之间的中位生存时间有显著差异(对数秩 P < 0.001)。荧光激活细胞分选分析显示,与短 RTL 组相比,长 RTL 组 CD4(+)T 细胞中 CD4(+)CD25(+)FOXP3(+)Treg 的百分比显著增加(P = 0.002)。总之,我们的研究结果表明,白细胞 RTL 可能是接受 TACE 治疗的 HCC 患者的独立预后标志物。