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Prediction of biomarkers for brain metastasis in nonsmall cell lung cancer based on transcriptome sequencing

Liangting Tan,Xuesong Xiang,Qiyi Qian,Qikun Zhang,Qiuran Xu,Wenhong Qiu,Xiaoliang Zheng

Published 2025 in Medicine

ABSTRACT

Background: Lung cancer is one of the most prevalent malignancies worldwide, and the metastasis of nonsmall cell lung cancer often leads to rapid deterioration of patient conditions, with brain metastasis (BM) being the most detrimental. The mechanisms underlying lung cancer brain metastasis remain incompletely understood. Objective: This study aimed to elucidate the molecular mechanisms of lung cancer brain metastasis and identify potential biomarkers and therapeutic targets. Methods: The high invasiveness of H1975-BM51 cells was verified using Western blotting, cell invasion assays, and the establishment of an nonsmall cell lung cancer brain metastasis mouse model. Transcriptome sequencing of H1975 and H1975-BM51 cells was conducted, followed by Least Absolute Shrinkage and Selection Operator regression and single-gene Gene Set Enrichment Analysis to screen key genes. Quantitative real-time PCR and Western blotting were employed to detect the expression levels of the AGO3 gene in H1975-BM51 cells. Results: Transcriptomic analysis revealed that the AGO3 gene contributes to lung cancer brain metastasis by negatively regulating hormone metabolic processes. Compared with parental H1975 cells, both mRNA and protein expression levels of AGO3 were significantly upregulated in highly invasive H1975-BM51 cells. Conclusion: This study identifies AGO3 as a potential biomarker and therapeutic target for lung cancer brain metastasis.

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