Expression and Prognostic Value of Brain and Acute Leukemia, Cytoplasmic in Meningiomas
Meningiomas are the most common central nervous system neoplasms, and their classification according to the World Health Organization (WHO) 2016 system divides them into three grades: grade I (benign), grade II (atypical), and grade III (anaplastic/malignant). While benign meningiomas are generally associated with a favorable prognosis, higher-grade meningiomas (grades II and III) are more aggressive and often result in less favorable outcomes. Understanding the molecular mechanisms underlying the progression and aggressiveness of meningiomas is crucial for improving prognostic accuracy and developing targeted therapies.
One molecule of interest in this context is brain and acute leukemia, cytoplasmic (BAALC). BAALC has previously been associated with poor prognosis in acute myeloid leukemia, and its potential role in meningiomas has recently been explored. This study aimed to investigate the expression and prognostic value of BAALC in meningiomas, focusing on its differential expression between low-grade and high-grade tumors and its potential as a biomarker for predicting patient outcomes.
The study included 82 meningioma patients who underwent surgery at Sir Run Run Shaw Hospital between 1999 and 2015. The cohort consisted of 39 patients with WHO grade I meningiomas (including subtypes such as meningothelial, fibrous, angiomatous, microcystic, secretory, and metaplastic), 34 patients with grade II meningiomas (primarily atypical and clear cell), and 9 patients with grade III meningiomas (including anaplastic, papillary, and rhabdoid subtypes). The patients were divided into two groups for analysis: low-grade meningiomas (grade I) and high-grade meningiomas (grades II and III).
Archival tissue blocks from these patients were used for histopathologic and immunohistochemical (IHC) analysis. The EnVision system was employed for IHC processing and staining, and primary antibodies against BAALC, progesterone receptor (PR), and Ki67 (MIB1) were used. BAALC expression was assessed using a semi-quantitative scoring system based on staining intensity and the percentage of positive cells. The staining intensity was scored as 0 (negative), 1 (weak), 2 (moderate), or 3 (strong), while the percentage of positive cells was scored as 0 (negative), 1 (0% to 25%), 2 (26% to 50%), or 3 (>50%).
The results revealed that BAALC expression varied significantly between low-grade and high-grade meningiomas. The average relative BAALC protein level was 2.51 ± 1.43 in low-grade meningiomas and 4.21 ± 1.51 in high-grade meningiomas, with the difference being statistically significant (P < 0.001). Additionally, BAALC expression was significantly associated with gender, tumor invasion, and brain invasion.
To evaluate the prognostic value of BAALC, the study analyzed its correlation with disease-specific survival (DSS) and progression-free survival (PFS) in the 82 meningioma patients. Univariate analysis demonstrated that tumor grade, BAALC levels, brain invasion, and necrosis were all significant prognostic factors for both DSS and PFS. Patients with higher BAALC expression had significantly worse DSS and PFS outcomes compared to those with lower BAALC expression.
To further explore the functional role of BAALC in meningiomas, the study conducted in vitro experiments using primary cultured meningioma cells. BAALC was overexpressed in these cells using a recombinant expression plasmid, and its effects on cell proliferation, migration, and invasion were assessed. The results showed that BAALC overexpression significantly promoted the proliferation of meningioma cells. In scratch wound healing assays, BAALC-overexpressing cells migrated to the wound edge at a faster rate and closed the wound area more quickly than control cells. Similarly, in transwell migration and invasion assays, BAALC-overexpressing cells exhibited significantly higher migration and invasion capabilities compared to control cells.
These findings suggest that BAALC plays a critical role in the malignant progression of meningiomas by promoting cell proliferation, migration, and invasion. The differential expression of BAALC between low-grade and high-grade meningiomas, as well as its significant prognostic value, highlights its potential as a biomarker for identifying high-risk patients and guiding treatment decisions.
In conclusion, this study provides compelling evidence that BAALC is a key molecular player in the progression of meningiomas. Its overexpression in high-grade tumors and its association with poor clinical outcomes underscore its potential as a prognostic marker. Furthermore, the functional experiments demonstrating BAALC’s role in promoting tumor cell proliferation, migration, and invasion offer insights into the molecular mechanisms underlying meningioma aggressiveness. Future studies should aim to validate these findings in larger cohorts and explore the therapeutic potential of targeting BAALC in meningiomas.
doi.org/10.1097/CM9.0000000000000398
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