DiaCarta Inc, Richmond, California, USA.
Department of Public Health, University Federico II of Naples, Naples, Italy.
J Clin Pathol. 2018 Dec;71(12):1123-1126. doi: 10.1136/jclinpath-2018-205412. Epub 2018 Oct 12.
Circulating cell free tumour derived nucleic acids are becoming recognised as clinically significant and extremely useful biomarkers for detection of cancer and for monitoring the progression of targeted drug therapy and immunotherapy. Screening programmes for colorectal cancer in Europe use the Fetal Immunochemical Test (FIT) test as a primary screener. FIT+ patients are referred to immediate colonoscopy and the positive predictive value (PPV) is usually 25%. In this article, we report a study employing the ColoScape assay panel to detect mutations in the APC, KRAS, BRAF and CTNNB1 genes, in order to collect preliminary performance indicators and plan a future, larger population study. The assay was evaluated on 52 prospectively collected whole-blood samples obtained from FIT+ patients enrolled in the CRC screening programme of ASL NAPOLI 3 SUD, using colonoscopy as confirmation. The assay's sensitivity for advanced adenomas was 53.8% and the specificity was 92.3%. The PPV was 70.0% and negative predicitive value (NPV) was 85.7%. Workflow optimisation is essential to maximise sensitivity. Of note, four of the six positive cases missed by ColoScape had a less than suboptimal DNA input (data not shown). Had they been ruled out as inadequate, sensitivity would have increased from 53.8% to 69%. However, as stated previously, this is not a clinical trial, but rather an initial, preliminary technical evaluation. In conclusion this study shows that ColoScape is a promising tool and further studies are warranted in order to validate its use for the triage of FIT+ patients.
循环肿瘤游离核酸正被认为是具有临床意义且非常有用的生物标志物，可用于检测癌症，并用于监测靶向药物治疗和免疫治疗的进展。欧洲的结直肠癌筛查计划使用胎儿免疫化学检测 (FIT) 作为主要筛查手段。FIT+患者被转介进行立即结肠镜检查，阳性预测值 (PPV) 通常为 25%。在本文中，我们报告了一项使用 ColoScape 检测 panel 检测 APC、KRAS、BRAF 和 CTNNB1 基因突变的研究，以收集初步的性能指标并计划进行未来更大规模的人群研究。该检测 panel 在来自 ASL NAPOLI 3 SUD 的 CRC 筛查计划中招募的 52 例前瞻性采集的全血样本中进行了评估，以结肠镜检查作为确认。该检测对高级腺瘤的敏感性为 53.8%，特异性为 92.3%。PPV 为 70.0%，阴性预测值 (NPV) 为 85.7%。优化工作流程对于提高敏感性至关重要。值得注意的是，ColoScape 漏诊的 6 例阳性病例中有 4 例 DNA 输入量不足（未显示数据）。如果将它们排除为不充分，则敏感性将从 53.8%提高到 69%。然而，如前所述，这不是临床试验，而是初步的技术评估。总之，本研究表明 ColoScape 是一种很有前途的工具，需要进一步研究以验证其在 FIT+患者中的分诊应用。
