Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China; Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China.
Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, PR China.
Lung Cancer. 2018 Jul;121:54-60. doi: 10.1016/j.lungcan.2018.05.002. Epub 2018 May 5.
Genetic profiles of primary and metastatic lung tumor have been investigated by previous studies. However, whether they can be replaced by each other to guide treatment remains controversial. Moreover, it is unclear that whether genetic profiles of plasma can reflect genetic divergence between primary and metastatic lesions.
In this prospective study, we collected 35 pairs of matched primary tumor tissue, metastatic lymph nodes and plasma from treatment-naïve patients with advanced non-squamous non-small cell lung cancer (NSCLC) and applied to capture-based sequencing using a panel consisting 56 NSCLC-related genes to interrogate the heterogeneity and similarity among the 3 sites.
We observed 62.0% (67/108) by-variant concordance rate among primary tumor, metastatic lymph nodes and plasma as well as 76.4% (81/106) by-variant concordance rate between primary tumor and metastatic lymph nodes. When the analysis restricted to driver genes, we achieved 60.9% (28/46) and 77.3% (34/44) concordance, respectively. Furthermore, there is no statistically significant difference in progression-free survival (PFS) of 17 patients who used matched targeted therapy between patients having 100% concordance rate between primary tumor and metastatic lymph nodes and patients having partially matched mutational profiles.
Collectively, our study revealed a similar genetic profile shared between primary tumor and metastatic lymph nodes. The limited discordance observed can be partially reflected by plasma. Sequencing results obtained from either site can be utilized for providing treatment guidance.
先前的研究已经调查了原发性和转移性肺肿瘤的基因谱。然而，它们是否可以相互替代来指导治疗仍存在争议。此外，尚不清楚血浆的基因谱是否能反映原发性和转移性病变之间的遗传差异。
在这项前瞻性研究中，我们收集了 35 对未经治疗的晚期非鳞状非小细胞肺癌（NSCLC）治疗的患者的配对原发性肿瘤组织、转移性淋巴结和血浆，并应用基于捕获的测序技术，使用包含 56 个 NSCLC 相关基因的面板来检测 3 个部位之间的异质性和相似性。
我们观察到原发性肿瘤、转移性淋巴结和血浆之间的 62.0%（67/108）的变异一致性，以及原发性肿瘤和转移性淋巴结之间的 76.4%（81/106）的变异一致性。当分析仅限于驱动基因时，我们分别达到了 60.9%（28/46）和 77.3%（34/44）的一致性。此外，在 17 名使用匹配靶向治疗的患者中，没有统计学意义的差异在无进展生存期（PFS）方面，原发性肿瘤和转移性淋巴结之间具有 100%一致性的患者和具有部分匹配突变谱的患者之间。
总之，我们的研究揭示了原发性肿瘤和转移性淋巴结之间存在相似的遗传谱。观察到的有限差异可以部分反映在血浆中。从任何部位获得的测序结果都可以用于提供治疗指导。
