as a potential biomarker for brain metastasis from lung adenocarcinoma via cerebrospinal fluid liquid biopsy.

BACKGROUND

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.