相对端粒长度：慢性乙型肝炎感染患者非肝硬化肝细胞癌风险的新型非侵入性生物标志物。
Relative telomere length: a novel non-invasive biomarker for the risk of non-cirrhotic hepatocellular carcinoma in patients with chronic hepatitis B infection.
机构信息
Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
出版信息
Eur J Cancer. 2012 May;48(7):1014-22. doi: 10.1016/j.ejca.2012.02.066. Epub 2012 Mar 21.
BACKGROUND AND AIMS
Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.
METHODS
We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.
RESULTS
Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls (median, 0.20; range, 0.01-1.60) (P = 0.003). Consistently, longer RTLs conferred a significantly increased HCC risk compared to short RTLs in a univariate logistic regression analysis (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.02-2.33, P = 0.038). This association attenuated after multivariate adjustment (OR = 1.40, 95% CI = 0.90-2.19, P = 0.132). In a quartile analysis, a significant dose-response relationship was noted in univariate analysis (P(trend) = 0.017) which was again attenuated in multivariate analysis (P(trend) = 0.079). Further analyses revealed that the significant association between serum RTL and HCC risk was evident in non-cirrhotic (OR = 3.54, 95% CI 1.58-7.93 P = 0.002), but not cirrhotic (OR = 0.95, 95% CI 0.55-1.64, P = 0.860) HBV patients. Moreover, the significantly increased HCC risk conferred by cirrhosis was modulated by RTL with a significant interaction effect (P(interaction) = 0.013).
CONCLUSIONS
RTL in circulating cell-free serum DNA could potentially be used as a novel non-invasive biomarker for non-cirrhotic HCC. Prospective cohort studies are warranted to validate this finding and assess its clinical significance in HCC prevention.
背景与目的
端粒长度已成为包括肝细胞癌（HCC）在内的各种癌症的有前途的风险预测因子。然而，该领域的大多数研究都是在肝细胞中测量端粒长度，而在淋巴细胞中仅测量了一项，结果相互矛盾。此外，尚无研究报道使用循环 DNA 端粒长度作为非侵入性 HCC 生物标志物。
方法
我们进行了一项巢式病例对照研究，以确定 140 例乙型肝炎病毒（HBV）相关 HCC 病例和 280 例频率匹配的无癌症 HBV 对照的血清 DNA 中的相对端粒长度（RTL）。
结果
与对照组（中位数 0.20；范围 0.01-1.60）相比，病例组的 RTL 明显更长（中位数 0.31；范围 0.02-2.31）（P = 0.003）。在单变量逻辑回归分析中，较长的 RTL 与较短的 RTL 相比，明显增加了 HCC 风险（优势比 [OR] = 1.55，95%置信区间 [CI] = 1.02-2.33，P = 0.038）。多变量调整后，这种关联减弱（OR = 1.40，95%CI = 0.90-2.19，P = 0.132）。在四分位数分析中，单变量分析中观察到显著的剂量反应关系（P（趋势）= 0.017），在多变量分析中再次减弱（P（趋势）= 0.079）。进一步的分析表明，血清 RTL 与 HCC 风险之间的显著关联在非肝硬化（OR = 3.54，95%CI 1.58-7.93，P = 0.002）但非肝硬化（OR = 0.95，95%CI 0.55-1.64，P = 0.860）HBV 患者中是明显的。此外，由肝硬化引起的 HCC 风险增加受到 RTL 的调节，其交互作用具有显著影响（P（交互）= 0.013）。
结论
循环无细胞血清 DNA 中的 RTL 可能可作为非肝硬化 HCC 的新型非侵入性生物标志物。需要前瞻性队列研究来验证这一发现，并评估其在 HCC 预防中的临床意义。
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