Yang Hainan, Wen Lei, Zhao Chao, Chen Jianing, Zhou Zhaoming, Zhou Cheng, Cai Linbo, Zhou Caicun
Department of Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai 200092, China.
Department of Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China.
Heliyon. 2022 Dec 16;8(12):e12374. doi: 10.1016/j.heliyon.2022.e12374. eCollection 2022 Dec.
Metastases to the central nervous system (CNS) are devastating neurological complications. Circulating cell-free tumor DNA (ctDNA) from cerebrospinal fluid (CSF) better represents genomic alterations in CNS tumors compared to plasma (PLA). However, the clinical value of cerebrospinal fluid (CSF) as a liquid biopsy medium in non-small cell lung cancer patients with leptomeningeal metastases (NSCLC-LM), regardless of extracranial evolution, remains unclear.
14/48 NSCLC-BM patients and 34/48 NSCLC-LM patients were enrolled in this study. The genomic mutation profiles in CSF and matched PLA for patients with single CNS progression (cohort one, N = 22) or intracranial progression with extracranial disease progression (cohort two, N = 12) were compared. ctDNA in the CSF and simultaneously collected PLA was subjected to next-generation target sequencing (NGS) of 168 cancer-relevant genes.
CSF is more comprehensive of driver genomic mutation profile than in matched PLA in patients with a single CNS progression. In addition, potential prognostic markers are much higher in CSF samples than related PLA. For example, the detection rate of -amp in CSF was more than twice of the rate in matched PLA. Moreover, , , and were detected uniquely in CSF samples and, all of these genetic mutations were correlated with poor outcomes.Almost all genetic mutation profiles detected in PLA could be seen in matched CSF samples in cohort two. With the driver genes, such as or have a higher detection rate in CSF compared to PLA. Moreover, the potential survival maker genes (6/12, 50%), (2/12, 17%), -amp (1/12, 8%), (1/12, 8%), and (1/12, 8%) were unique to the CSF samples.
For NSCLC -LM patients, regardless of single intracranial progression or intracranial progression simultaneously with extracranial evolution, CSF is superior to matched PLA.
中枢神经系统（CNS）转移是严重的神经系统并发症。与血浆（PLA）相比，脑脊液（CSF）中的循环游离肿瘤DNA（ctDNA）能更好地反映CNS肿瘤中的基因组改变。然而，对于有软脑膜转移的非小细胞肺癌患者（NSCLC-LM），无论颅外病情如何发展，脑脊液（CSF）作为液体活检介质的临床价值仍不明确。
本研究纳入了48例NSCLC-BM患者中的14例以及48例NSCLC-LM患者中的34例。比较了单发性CNS进展患者（队列一，N = 22）或伴有颅外疾病进展的颅内进展患者（队列二，N = 12）脑脊液和匹配血浆中的基因组突变谱。对脑脊液和同时采集的血浆中的ctDNA进行168个癌症相关基因的二代靶向测序（NGS）。
在单发性CNS进展患者中，脑脊液中的驱动基因组突变谱比匹配血浆中的更全面。此外，脑脊液样本中的潜在预后标志物比相关血浆中的高得多。例如，脑脊液中-amp的检测率是匹配血浆中检测率的两倍多。此外， 、 、 和 仅在脑脊液样本中被检测到，所有这些基因突变都与不良预后相关。在队列二中，血浆中检测到的几乎所有基因突变谱在匹配的脑脊液样本中都能看到。对于驱动基因，如 或 ，脑脊液中的检测率高于血浆。此外，潜在的生存标志物基因 （6/12，50%）、 （2/12，17%）、-amp（1/12，8%）、 （1/12，8%）和 （1/12，8%）在脑脊液样本中是独特的。
对于NSCLC-LM患者，无论颅内是单发性进展还是与颅外进展同时发生，脑脊液均优于匹配的血浆。
