Abstract
Meningiomas are primary central nervous system (CNS) tumors that originate from the arachnoid cells of the meninges. Recurrence occurs in higher grade meningiomas and a small subset of Grade I meningiomas with benign histology. Currently, there are no established circulating tumor markers which can be used for diagnostic and prognostic purposes in a non-invasive way for meningiomas. Here, we aimed to identify potential biomarkers of meningioma in patient sera. For this purpose, we collected preoperative (n = 30) serum samples from the meningioma patients classified as Grade I (n = 23), Grade II (n = 4), or Grade III (n = 3). We used a high-throughput, multiplex immunoassay cancer panel comprising of 92 cancer-related protein biomarkers to explore the serum protein profiles of meningioma patients. We detected 14 differentially expressed proteins in the sera of the Grade I meningioma patients in comparison to the age- and gender-matched control subjects (n = 12). Compared to the control group, Grade I meningioma patients showed increased serum levels of amphiregulin (AREG), CCL24, CD69, prolactin, EGF, HB-EGF, caspase-3, and decreased levels of VEGFD, TGF-α, E-Selectin, BAFF, IL-12, CCL9, and GH. For validation studies, we utilized an independent set of meningioma tumor tissue samples (Grade I, n = 20; Grade II, n = 10; Grade III, n = 6), and found that the expressions of amphiregulin and Caspase3 are significantly increased in all grades of meningiomas either at the transcriptional or protein level, respectively. In contrast, the gene expression of VEGF-D was significantly lower in Grade I meningioma tissue samples. Taken together, our study identifies a meningioma-specific protein signature in blood circulation of meningioma patients and highlights the importance of equilibrium between tumor-promoting factors and anti-tumor immunity.
Highlights
Meningiomas account for 53.1% of all non-malignant brain and other central nervous system (CNS) tumors [1]
Our results showed that 14 proteins were differentially expressed in the Grade I meningioma patients compared to healthy control subjects (Figure 1)
Seven proteins, caspase-3, CD69, prolactin, epidermal growth factor (EGF), chemokine (C-C) ligand 24 (CCL24), amphiregulin (AREG), and heparin-binding EGF (HB-EGF) were highly expressed in the Grade I meningioma samples (Figure 1B), while, the other seven proteins, vascular endothelial growth factor D (VEGFD), transforming growth factor alpha (TGF-α), E-selectin, Bcell activating factor (BAFF), interleukin-12 (IL-12), chemokine (C-C motif) ligand 9 (CCL9), and Growth Hormone were reduced in the meningioma serum samples, compared to healthy control subjects (Figure 1C and Table 1)
Summary
The majority of meningiomas with documented WHO grade is Grade I (80.6%) [1]. These benign tumors can remain dormant without causing any symptoms for a long time, which arguably represents the major challenge in early detection of meningiomas [2]. Recurrence frequently occurs in tumors with benign histology, and recent studies revealed that coexistence of del(1p36) and monosomy 14 is associated with early recurrence of meningiomas [3]. Recent studies showed that other genetic alterations in TRAF7, PIK3CA, KLF4, POLR2A AKT1, SMO, SUFU, and SMARCB1 genes are involved in meningioma pathogenesis [5,6,7,8]. Treatment protocol for meningomas is closely associated with tumor location, grade and includes surgery followed by fractionated external beam radiation therapy (EBRT) [10]
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