Breakthrough in treating recurrent brain tumors through precision genomic analysis

A research team led by Professor Jason Kyungha Sa from the Department of Biomedical Informatics at Korea University College of Medicine has identified a novel therapeutic target for recurrent meningioma through precision genomic analysis.

By performing single-cell RNA profiling of recurrent meningiomas, the team systematically mapped the tumor’s evolutionary process and its interactions with surrounding immune cells. The study revealed that the COL6A3 gene is a key driver of recurrence risk and a promising therapeutic target.

Meningiomas account for approximately 30% of all brain tumors and are generally classified as benign tumors. However, high-grade or recurrent meningiomas are notoriously difficult to treat and are associated with poor prognoses.

Until now, few studies have precisely compared primary and recurrent tumors from the same patient at the single-cell resolution to track the tumor evolutionary pattern. To address this gap, Professor Sa’s team conducted single-nuclei RNA sequencing (snRNA-seq) on matched primary and recurrent tumors from Korean meningioma patients.

Their results showed that recurrent meningiomas exhibit accelerated cell proliferation and increased COL6A3 expression. By tracing tumor transcriptional changes over time and performing cellular interaction analysis, the team found that COL6A3 was increasingly activated in the later stages of tumor progression. Moreover, it interacts with immunosuppressive macrophages, facilitating malignant transformation.

Further analysis between the meningioma risk prediction index and COL6A3 expression confirmed that overexpression of COL6A3 significantly increases tumor malignancy. In an independent dataset of 110 meningioma patients, those with high COL6A3 expression showed markedly higher recurrence rates.

“This study is significant as it precisely compared primary and recurrent tumors from the same patient using single-cell transcriptomics, revealing how meningiomas evolve and interact with the tumor microenvironment,” said Professor Sa. “For recurrent meningiomas, where treatment options are limited, our findings provide a crucial starting point for developing new therapeutic strategies targeting COL6A3.”

The results were published in the journal Nature Communications (Impact Factor: 15.7) under the title “Single-cell analysis reveals a longitudinal trajectory of meningioma evolution and heterogeneity.”