Tang Yong, Liu Xianling, Ou Zhu'An, He Zhe, Zhu Qihang, Wang Ye, Yang Mei, Ye Junyi, Han-Zhang Han, Qiao Guibin
Department of Thoracic Surgery, General Hospital of Southern Theater Command, Guangzhou, Guangdong 510010, P.R. China.
Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Oncol Lett. 2019 Aug;18(2):2118-2124. doi: 10.3892/ol.2019.10490. Epub 2019 Jun 18.
Personalized medicine is revolutionizing the diagnosis and treatment of cancer; however, for personalized medicine to be used accurately, patient information is essential to determine the appropriate diagnosis, prognosis and treatment. The detection of genomic mutations in liquid biopsy samples is a non-invasive method of characterizing the genotype of a tumor. However, next generation sequencing-based plasma genotyping only has a sensitivity of ~70%. Identifying potential indicators that may reflect the sensitivity of a liquid biopsy analysis could offer important information for its clinical application. In the present study, 47 pairs of patient-matched plasma and tumor tissue samples obtained from patients with advanced lung cancer were sequenced using a panel of 56 cancer-associated genes. The plasma maximum allele frequency (Max AF) was identified as a novel biomarker to indicate the sensitivity of plasma genotyping. Using the identified somatic mutations in patient tissue biopsy samples as a reference, the sensitivity of the corresponding patient plasma test was investigated. The by-variant sensitivity of the plasma test was 68.1%, with 79 matched and 37 missed genetic aberrances. The by-patient sensitivity was calculated as 83%. Patients with a high plasma Max AF value (>2.2%) demonstrated a higher concordance with the range of mutations identified in the patient-matched tissue samples. The Max AF observed in patient plasma samples was positively correlated with liquid biopsy sensitivity and could be used as a potential indicator of liquid biopsy sensitivity. Therefore, patients with a low plasma Max AF (≤2.2%) may need to undergo further tissue biopsy to allow personalized oncology treatment. In summary, the present study may offer a non-invasive testing method for a sub-group of patients with advanced lung cancer.
个性化医疗正在彻底改变癌症的诊断和治疗；然而，为了准确使用个性化医疗，患者信息对于确定合适的诊断、预后和治疗至关重要。在液体活检样本中检测基因组突变是一种表征肿瘤基因型的非侵入性方法。然而，基于下一代测序的血浆基因分型的灵敏度仅约为70%。识别可能反映液体活检分析灵敏度的潜在指标可为其临床应用提供重要信息。在本研究中，使用一组56个癌症相关基因对从晚期肺癌患者获得的47对患者匹配的血浆和肿瘤组织样本进行了测序。血浆最大等位基因频率（Max AF）被确定为一种新的生物标志物，可指示血浆基因分型的灵敏度。以患者组织活检样本中识别出的体细胞突变为参考，研究了相应患者血浆检测的灵敏度。血浆检测的逐变体灵敏度为68.1%，有79个匹配的和37个遗漏的基因异常。逐患者灵敏度计算为83%。血浆Max AF值高（>2.2%）的患者与患者匹配组织样本中识别出的突变范围具有更高的一致性。在患者血浆样本中观察到的Max AF与液体活检灵敏度呈正相关，可作为液体活检灵敏度的潜在指标。因此，血浆Max AF低（≤2.2%）的患者可能需要接受进一步的组织活检，以实现个性化肿瘤治疗。总之，本研究可能为晚期肺癌患者亚组提供一种非侵入性检测方法。
