Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan,
Oncology. 2020;98(5):311-317. doi: 10.1159/000506135. Epub 2020 Mar 5.
Mutations in the human telomerase reverse transcriptase (hTERT) gene promoter have been reported in hepatocellular carcinoma (HCC); however, analyses of these mutations in liquid biopsies have been technically difficult because of the high GC content of the regions of interest within this promoter. We evaluated the feasibility and prognostic value of hTERT promoter mutations identified in circulating cell-free DNA (cfDNA) from the serum of patients with HCC.
A cohort of HCC patients (n = 36) who were curatively treated by surgical resection between June 2003 and September 2014 were enrolled in this study.
The presence of hTERT promoter mutations in cfDNA from the patients' serum was analyzed via modified droplet digital polymerase chain reaction, and associations were sought between specific promoter mutations and patients' disease-free survival (DFS).
The G>A hTERT mutation at -124 bp was detected in the serum of 25 patients (69%). Although no marked differences were observed between the characteristics of the serum mutation-positive and serum mutation-negative patient groups, the DFS of patients with the mutation was significantly shorter than that of the serum mutation-negative patients (p = 0.02). Among 18 clinicopathologic and background liver factors examined, the presence of the -124 bp G>A mutation was an independent and significant predictor of patients' DFS (hazard ratio = 3.01, 95% confidence interval 1.11-10.5, p = 0.03) in multivariate analyses.
The -124 bp G>A hTERT promoter mutation was observed in the serum of 69% of HCC patients who underwent surgical resection and was an independent predictor of disease progression in HCC.
已报道人类端粒酶逆转录酶（hTERT）基因启动子中的突变与肝细胞癌（HCC）有关；然而，由于该启动子中感兴趣区域的高 GC 含量，对这些突变在液体活检中的分析在技术上具有挑战性。我们评估了在接受根治性手术切除的 HCC 患者血清中循环无细胞 DNA（cfDNA）中鉴定的 hTERT 启动子突变的可行性和预后价值。
本研究纳入了 2003 年 6 月至 2014 年 9 月间接受根治性手术切除的 HCC 患者队列（n=36）。
通过改良的液滴数字聚合酶链反应分析患者血清中 cfDNA 中 hTERT 启动子突变的存在，并探讨特定启动子突变与患者无病生存期（DFS）之间的关系。
在 25 名患者（69%）的血清中检测到 -124 bp 的 G>A hTERT 突变。尽管血清突变阳性和血清突变阴性患者组的特征之间未观察到明显差异，但突变患者的 DFS 明显短于血清突变阴性患者（p=0.02）。在检查的 18 个临床病理和背景肝脏因素中，-124 bp G>A 突变的存在是患者 DFS 的独立和显著预测因素（风险比=3.01，95%置信区间 1.11-10.5，p=0.03）。
在接受手术切除的 HCC 患者的血清中观察到 -124 bp G>A hTERT 启动子突变，是 HCC 疾病进展的独立预测因素。
