Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, China.
Key Laboratory of Chest Cancer, Shandong University, Jinan, China.
Thorac Cancer. 2021 Jan;12(2):181-193. doi: 10.1111/1759-7714.13741. Epub 2020 Nov 16.
To distinguish early-stage lung cancer from benign disease in pulmonary nodules, especially lesions with ground-glass opacity (GGO), we assessed gene mutations of ctDNA in peripheral blood using targeted next-generation sequencing (NGS).
Single pulmonary nodule patients without mediastinal lymph nodes and symptoms that were hard to diagnose by chest CT and lung cancer biomarker measurement in multiple medical centers were enrolled into the study. All patients accepted minimally invasive surgery but refused preoperative biopsy. Gene mutations in preoperative blood samples were detected by targeted NGS. Mutations with significant differences between lung tumors and benign lesions, as grouped by postoperative pathology, were screened. Protein expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood.
In the training set, the RNF213, KMT2D, CSMD3 and LRP1B genes were mutated more frequently in early-stage lung cancer (27 cases) than in benign nodules (15 cases) (P < 0.05). High expression of the RNF213 gene in lung cancers and low expression in benign diseases were seen by immunohistochemistry. The RNF213 gene was mutated in 25% of lung cancer samples in the validation set of 28 samples and showed high specificity (100%). In GGO patients, RNF213 was mutated more frequently in early-stage lung cancer compared to benign diseases (P < 0.05).
RNF213 gene mutations were observed more frequently in early-stage lung cancer, but not in benign nodules. Mutation of the RNF213 gene in peripheral blood may be a high specificity biomarker for the assisted early diagnosis of lung cancer in pulmonary nodules.
Significant findings of the study: In peripheral venous blood and tumor tissue, RNF213 gene mutated more frequently in lung cancer than benign pulmonary nodules.
Detection mutation of the RNF213 gene in peripheral blood may be a high specificity method for the assisted early diagnosis of lung cancer in pulmonary nodules.
为了区分肺部结节中的早期肺癌和良性病变，特别是磨玻璃密度（GGO）病变，我们使用靶向下一代测序（NGS）评估了外周血中的 ctDNA 基因突变。
本研究纳入了来自多个医疗中心的经胸部 CT 和肺癌标志物测量难以诊断的孤立性肺结节患者。所有患者均接受了微创外科手术，但拒绝了术前活检。通过靶向 NGS 检测术前血液样本中的基因突变。筛选出术后病理分组中肺部肿瘤与良性病变之间存在显著差异的突变。通过免疫组织化学法确定蛋白质表达。选择高表达基因作为外周血突变的验证标志物。
在训练集中，RNF213、KMT2D、CSMD3 和 LRP1B 基因突变在 27 例早期肺癌（27 例）中比在 15 例良性结节（15 例）中更常见（P<0.05）。通过免疫组织化学法观察到 RNF213 基因在肺癌中高表达，在良性疾病中低表达。在 28 例验证集中，25%的肺癌样本中 RNF213 基因发生突变，具有很高的特异性（100%）。在 GGO 患者中，早期肺癌中 RNF213 基因突变的频率高于良性疾病（P<0.05）。
在早期肺癌中观察到 RNF213 基因突变的频率高于良性结节，但未在良性结节中观察到。外周血中 RNF213 基因突变可能是肺部结节辅助早期诊断肺癌的高特异性生物标志物。
研究的重要发现：在外周静脉血和肿瘤组织中，RNF213 基因突变在肺癌中比良性肺结节中更常见。
外周血中 RNF213 基因突变的检测可能是肺部结节辅助早期诊断肺癌的一种高特异性方法。
