Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer
Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer
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DOI：
10.1007/s12253-020-00819-x
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发表时间：
2020-05-27
影响因子：
2.8
通讯作者：
Lippi, Giuseppe
中科院分区：
文献类型：
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作者：
Benati, Marco;Montagnana, Martina;Lippi, Giuseppe
探讨游离DNA(CfDNA)相对端粒长度(RTL)对子宫内膜样癌(EC)的诊断价值。我们测定了40例EC患者(65+/-12岁)和31例健康对照(HC)(63+/-13岁)cfDNA中的RTL，排除了两组中的其他肿瘤和严重的非肿瘤疾病，以限制混杂因素。使用QIAamp DNA血液迷你试剂盒(德国希尔登的Qigen)从血清中提取循环cfDNA。实时定量聚合酶链式反应后，计算端粒重复拷贝数与单基因拷贝数之比。CfDNA中的rtl在EC组显著低于HC组(p<；0.0001)。CfDNARTL的诊断准确率为0.87(95%CI：0.79~0.95，p<；0.0001)。CfDNARTL值为2.505(T/S拷贝比)的敏感性为80.0%(95%CI：64.35~90.95)，特异性为80.65%(95%CI：62.53~92.55)。不同EC分期和分级的RTL差异无统计学意义(p=0.85和p=0.89)。我们的结果表明，cfDNA RTL分析可能是早期检测EC的一种诊断工具，而它在癌症进展、分期和分级方面的诊断性能似乎并不令人满意。然而，还需要进一步的研究来证实这些初步发现。特别是，未来的研究应该集中在可能受益于该工具的高危患者(如那些患有非典型子宫内膜增生症的患者)，因为TL缩短不是EC所特有的，而且受到其他肿瘤性和非肿瘤性疾病的影响。
To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 +/- 12 years) and 31 healthy controls (HC) (63 +/- 13 years), excluding in both groups other oncologic and severe non-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than in HC (p < 0.0001). The diagnostic performance of cfDNA RTL was estimated with receiver operating characteristics (ROC) curve analysis, which showed a diagnostic accuracy for EC of 0.87 (95% CI: 0.79-0.95,p < 0.0001). The cutoff cfDNA RTL value of 2.505 (T/S copy ratio) reported a sensitivity of 80.0% (95% CI: 64.35-90.95) and a specificity of 80.65% (95% CI: 62.53-92.55). Significant differences of RTL among EC stages or grades (p = 0.85 andp = 0.89, respectively) were not observed. Our results suggest that cfDNA RTL analysis may be a diagnostic tool for EC detection since the early stage, whilst its diagnostic performance seems unsatisfactory for cancer progression, staging, and grading. However, further studies are needed to confirm these preliminary findings. In particular, future investigations should focus on high-risk patients (such as those with atypical endometrial hyperplasia) that may benefit from this tool, because TL shortening is not specific for EC and is influenced by other oncologic and non-oncologic diseases.