Sun Qinhong, Xing Peng, Wang Qinglin, Xia Zhijun, Li Jianyu, Li Zhitong, Meng Fancheng, Liu Tongyan, Wang Siwei, Yin Rong
Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China.
Department of Oncology, Jing County Hospital, Xuancheng, China.
Transl Lung Cancer Res. 2025 Mar 31;14(3):662-676. doi: 10.21037/tlcr-24-800. Epub 2025 Mar 3.
Brain metastasis (BM) explains the majority of lung cancer-related mortality, especially lung adenocarcinoma (LUAD). The extensive clinical adoption of liquid biopsy presents a minimally invasive approach for the early detection and treatment management of brain metastasis from lung adenocarcinoma (BM-LUAD). Nonetheless, biomarkers for assessing BM-LUAD remain insufficient. This study aims to reveal novel biomarkers for BM-LUAD through the liquid biopsy of cerebrospinal fluid (CSF).
Circulating tumor DNA (ctDNA)-based panel sequencing was conducted on CSF samples from seven patients with BM-LUAD. Additionally, single-cell RNA sequencing (scRNA-seq) data from normal lung tissue, primary tumors, and BMs were analyzed using publicly available datasets. Functional assays were performed on cell lines, complemented by studies in nude mice.
CSF liquid biopsy identified high-frequency mutations in , and among patients with BM-LUAD. Further analysis highlighted as a potential biomarker, showing reduced expression in tumor tissues and significant prognostic implications. ScRNA-seq revealed a progressive decrease in expression along tumor progression, while and assays confirmed its role in suppressing tumor invasion and metastasis.
Our study highlights the potential of ctDNA-based CSF liquid biopsy in identifying BM-LUAD, and the efficacy in revealing novel biomarkers for BM-LUAD. Data analyses and functional assays indicated as a predictive biomarker for BM-LUAD. This result addresses, to some extent, the existing gap in biomarkers for BM-LUAD.
脑转移（BM）是大多数肺癌相关死亡的原因，尤其是肺腺癌（LUAD）。液体活检在临床上的广泛应用为肺腺癌脑转移（BM-LUAD）的早期检测和治疗管理提供了一种微创方法。然而，用于评估BM-LUAD的生物标志物仍然不足。本研究旨在通过脑脊液（CSF）液体活检揭示BM-LUAD的新型生物标志物。
对7例BM-LUAD患者的脑脊液样本进行基于循环肿瘤DNA（ctDNA）的panel测序。此外，使用公开可用的数据集分析来自正常肺组织、原发性肿瘤和脑转移灶的单细胞RNA测序（scRNA-seq）数据。对细胞系进行功能测定，并辅以裸鼠研究。
脑脊液液体活检在BM-LUAD患者中发现了 、 和 中的高频突变。进一步分析突出显示 作为一种潜在的生物标志物，在肿瘤组织中表达降低并具有显著的预后意义。ScRNA-seq显示 表达随肿瘤进展逐渐降低，而 和 测定证实了其在抑制肿瘤侵袭和转移中的作用。
我们的研究突出了基于ctDNA的脑脊液液体活检在识别BM-LUAD方面的潜力，以及在揭示BM-LUAD新型生物标志物方面的功效。数据分析和功能测定表明 是BM-LUAD的预测性生物标志物。这一结果在一定程度上填补了BM-LUAD生物标志物方面的现有空白。
