Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.
Division of Thoracic Oncology, West German Cancer Center, University Medicine Essen Ruhrlandklinik, University Duisburg-Essen, Essen, Germany.
Thorac Cancer. 2022 Aug;13(15):2180-2191. doi: 10.1111/1759-7714.14540. Epub 2022 Jun 16.
CT scans are used in routine clinical practice for the diagnosis and treatment surveillance of non-small cell lung cancer (NSCLC). However, more sensitive methods are desirable. Liquid biopsy analyses of RNA and DNA can offer more sensitive diagnostic approaches. Cell-free RNA (cfRNA) has been described in several malignancies, but its clinical utility has not previously been explored.
We evaluated the clinical utility of cfRNA for early detection and surveillance of tumor disease in a proof-of-concept study. Using real-time-droplet digital polymerase chain reaction we characterized a candidate transcript (MORF4L2) in plasma samples from 41 advanced stage, 38 early stage NSCLC and 39 healthy samples. We compared its diagnostic performance with tumor markers and evaluated its utility for disease monitoring.
MORF4L2 cfRNA was more abundant in patients than in healthy donors (p < 0.0001). Using the Youden index approach (cutoff value of 537 copies/ml was established) with a sensitivity of 0.73 (95% CI: 0.61-0.82) and a specificity of 0.87 (95% CI: 0.73-0.96). Positive and negative predictive values of 0.92 (95% CI: 0.83-0.95) and 0.59 (95% CI: 0.47-0.83) were achieved. Combination of cfRNA and Cyfra21-1 improved its predictive value from 89.5% to 94.7%. Low baseline MORF4L2 levels were associated with better overall survival (HR:0.25, 95% CI: 0.09-0.7, p = 0.009) and progression-free survival for patients treated with tyrosine kinase inhibitors (p = 0.011) and chemotherapy (p = 0.019). MORF4L2 profile between baseline and follow-up mirrored radiological response and tumor dynamics better than tumor markers. cfRNA transcripts allowed monitoring tumor dynamics in patients without tumor-reported genetic alterations.
Our data support clinical utility of cfRNA for detection and surveillance of NSCLC. Further studies with larger cohorts are required.
CT 扫描在非小细胞肺癌（NSCLC）的诊断和治疗监测中常规应用于临床实践。然而，人们希望使用更敏感的方法。RNA 和 DNA 的液体活检分析可以提供更敏感的诊断方法。在几种恶性肿瘤中已经描述了无细胞 RNA（cfRNA），但尚未探索其临床应用。
我们在一项概念验证研究中评估了 cfRNA 用于早期检测和监测肿瘤疾病的临床应用。使用实时液滴数字聚合酶链反应，我们对 41 名晚期、38 名早期 NSCLC 患者和 39 名健康样本的血浆样本中的候选转录物（MORF4L2）进行了特征描述。我们比较了其与肿瘤标志物的诊断性能，并评估了其用于疾病监测的效用。
MORF4L2 cfRNA 在患者中的丰度高于健康供体（p<0.0001）。使用约登指数法（建立的截断值为 537 拷贝/ml），其敏感性为 0.73（95%CI：0.61-0.82），特异性为 0.87（95%CI：0.73-0.96）。阳性和阴性预测值分别为 0.92（95%CI：0.83-0.95）和 0.59（95%CI：0.47-0.83）。cfRNA 与 Cyfra21-1 联合使用可将其预测值从 89.5%提高至 94.7%。基线 MORF4L2 水平较低与接受酪氨酸激酶抑制剂（HR：0.25，95%CI：0.09-0.7，p=0.009）和化疗（p=0.019）治疗的患者的总体生存（HR：0.25，95%CI：0.09-0.7，p=0.009）和无进展生存改善相关。MORF4L2 谱在基线和随访之间与影像学反应和肿瘤动力学的匹配优于肿瘤标志物。cfRNA 转录本允许在没有肿瘤报告遗传改变的患者中监测肿瘤动力学。
我们的数据支持 cfRNA 用于 NSCLC 的检测和监测的临床应用。需要更大队列的进一步研究。
