ANKRD11 as a potential biomarker for brain metastasis from lung adenocarcinoma via cerebrospinal fluid liquid biopsy.

Abstract

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 in vivo studies in nude mice.

Results: CSF liquid biopsy identified high-frequency mutations in EGFR, BRCA2, and ANKRD11 among patients with BM-LUAD. Further analysis highlighted ANKRD11 as a potential biomarker, showing reduced expression in tumor tissues and significant prognostic implications. ScRNA-seq revealed a progressive decrease in ANKRD11 expression along tumor progression, while in vitro and in vivo 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 ANKRD11 as a predictive biomarker for BM-LUAD. This result addresses, to some extent, the existing gap in biomarkers for BM-LUAD.