Expression and Prognostic Value of Brain and Acute Leukemia, Cytoplasmic (BAALC) in Meningiomas
Meningiomas are the most common primary brain tumors, affecting about 3 in 100,000 people annually. While most are benign (WHO grade I), higher-grade tumors (grades II and III) are aggressive—more likely to recur, invade brain tissue, and reduce survival. Now, a 2019 study from Chinese researchers highlights a protein called brain and acute leukemia, cytoplasmic (BAALC) that could help predict outcomes and unlock new ways to treat these challenging tumors.
Led by Yong-Tao He from the Department of Pathology at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and Qiao Zhou from West China Hospital, Sichuan University, the team analyzed 82 meningioma samples from patients treated between 1999 and 2015. The goal? To explore how BAALC—already linked to poor prognosis in acute myeloid leukemia—behaves in meningiomas and whether it influences tumor growth.
What Is BAALC, and Why Does It Matter?
BAALC is a protein involved in cell growth and migration. Previous research using gene expression profiling (a tool to map which genes are active in tumors) found BAALC was 4.76 times more active in high-grade meningiomas than benign ones. This study aimed to confirm BAALC’s role at the protein level—and its impact on patient survival.
How the Study Worked
The team used two key approaches:
- Tissue Analysis: They tested 82 meningioma samples (39 grade I, 34 grade II, 9 grade III) using immunohistochemistry (IHC)—a technique to visualize BAALC protein in tumor cells. BAALC staining was scored based on intensity (0 = negative, 3 = strong) and percentage of positive cells (0 = none, 3 = over 50%).
- Cell Experiments: They grew primary meningioma cells in the lab, overexpressed BAALC, and measured effects on proliferation (cell growth), migration (movement), and invasion (spreading through tissue). Tests included:
- Cell Counting Kit-8 (CCK-8): Tracks viable cell numbers over time.
- Scratch Wound Healing: Measures how quickly cells close a “wound” in a monolayer.
- Transwell Assays: Tests if cells can migrate through a membrane (migration) or invade a Matrigel layer (mimicking brain tissue).
Key Findings
The results painted a clear picture of BAALC’s role in meningioma progression:
1. BAALC Is Higher in Aggressive Meningiomas
BAALC protein levels were significantly higher in high-grade (grades II/III) tumors compared to low-grade (grade I) ones. The average score for high-grade meningiomas was 4.21, vs. 2.51 for low-grade—an difference that was statistically meaningful (P < 0.001). BAALC was also more common in tumors that invaded brain tissue and in male patients.
2. BAALC Predicts Worse Survival
Patients with high BAALC levels had shorter disease-specific survival (DSS) (time until death from meningioma) and progression-free survival (PFS) (time until tumor recurrence or growth). Other factors linked to poor outcomes included higher tumor grade, brain invasion, and tumor necrosis (tissue death).
3. BAALC Drives Tumor Growth and Spread
Lab experiments confirmed BAALC’s active role in meningioma biology:
- Proliferation: Cells overexpressing BAALC grew faster than control cells (measured by CCK-8 absorbance at 570 nm).
- Migration: BAALC-overexpressing cells closed scratch wounds in 72 hours—twice as fast as controls. In transwell migration assays, 1,000 BAALC-positive cells moved through a membrane per field of view, vs. 600 control cells.
- Invasion: BAALC-overexpressing cells were 1.8 times more likely to invade Matrigel (1,300 cells per field vs. 700 controls).
What This Means for Patients and Doctors
The study adds two critical insights to meningioma research:
- Prognostic Marker: BAALC could help doctors identify patients at higher risk of recurrence or worse outcomes—even among grade II/III tumors. This might guide more aggressive follow-up or treatment.
- Therapeutic Target: Since BAALC promotes tumor growth and spread, blocking it could be a new strategy for high-grade meningiomas. Current treatments (surgery, radiation) are limited for aggressive tumors, so targeted therapies are urgently needed.
The Bigger Picture
This work builds on decades of research using gene expression profiling to unlock meningioma biology. For example, earlier studies identified molecular differences between benign and malignant tumors, but this is one of the first to link BAALC protein levels to real-world patient outcomes.
All procedures followed ethical guidelines (1964 Helsinki Declaration), and patients gave informed consent. The study was funded by the Natural Science Foundation of Zhejiang Province (LQ13H160007).
Published in the Chinese Medical Journal in 2019, the research offers a new piece of the puzzle for understanding—and eventually beating—aggressive meningiomas.
doi.org/10.1097/CM9.0000000000000398
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