Proteomics pinpoints alterations in grade I meningiomas of male versus female patients

Abstract

Meningiomas are among the most common primary tumors of the central nervous system (cnS) and originate from the arachnoid or meningothelial cells of the meninges. Surgery is the first option of treatment, but depending on the location and invasion patterns, complete removal of the tumor is not always feasible. Reports indicate many differences in meningiomas from male versus female patients; for example, incidence is higher in females, whereas males usually develop the malignant and more aggressive type. With this as motivation, we used shotgun proteomics to compare the proteomic profile of grade I meningioma biopsies of male and female patients. Our results listed several differentially abundant proteins between the two groups; some examples are S100-A4 and proteins involved in RNA splicing events. For males, we identified enriched pathways for cell-matrix organization and for females, pathways related to RNA transporting and processing. We believe our findings contribute to the understanding of the molecular differences between grade I meningiomas of female and male patients. Meningioma is a high incidence tumor that typically emerges at the arachnoid cap or meningothelial cells of the meninges 1 , commonly from intracranial, intraspinal, or orbital locations, and are usually benign, slow-growing tumors 2. Resonance imaging and molecular markers are frequently used for preliminary diagnosis; yet, surgical removal of the tumor is necessary for histological diagnostic confirmation and improved life quality 1,2. When surgery for total removal of the tumor is not feasible, adjuvant radiation may be used 1. The World Health Organization (WHO) classifies meningiomas according to their histopathological characteristics, mitotic count, and brain invasion pattern in (i) grade I, also known as benign meningiomas (BMs, about 80% of termed cases); (ii) grade II, or atypical meningiomas (AMs, 17% of termed cases); and (iii) grade III, the malignant meningiomas (MMs, 3% of termed cases) 3. Although this classification is valid in terms of prognosis, it lacks information about tumor aggressiveness and recurrence rates 2. Controversially, most recurrent meningiomas correspond to BMs; their metabolic phenotype indicates an aggressive metabolism, resembling that of AM 4. Female patients present approximately double the incidence of meningiomas compared to men 1. Interestingly, the main risk factor for meningiomas is related to hormonal changes as these tumors present hormones receptors (i.e., progesterone and estrogen) 5,6. Moreover, association between meningiomas and breast cancer, mainly due to similar hormonal signaling and genetic predisposition, has also been reported 5. The fact that women diagnosed with breast cancer are more likely to develop meningioma may also justify the higher incidence of this tumor in females 7,8. In general, women usually develop the benign form while males develop the malignant type of meningioma, the aggressive grade III 6. Besides gender, other risk factors associated with this disease include...

Advances in meningioma genomics, proteomics, and epigenetics: insights into biomarker identification and targeted therapies

“…Shotgun proteomics has also demonstrated differences in grade 1 meningiomas presenting in different genders. Differences in RNA splicing events (S100-A4) were observed between the two groups, with males exhibiting enriched pathways for cell-matrix organization and females exhibiting enriched pathways for RNA transport and processing [52]. Further proteomics studies have been able to narrow down which proteins may serve as a potential therapeutic target.…”

Giant Skull Tumor: A Benign Meningioma

“…Mukhopadhyay et al 4 Found that 96.34% of grade I meningioma are positive for progesterone immunostain as our case that shows moderate nuclear positivity along with morphological findings encourage the diagnosis of grade I meningioma. Silva et al 5 Compared the incidence and the behavior of grade I meningioma according to different genders that it is more common in females, whereas it has more aggressive behavior in males due to the presence of enriched pathways in the male group that related to extracellular matrix organization. This supports the aggressive extension in our male patient.…”

Malignant meningioma

“…To this date, few studies investigated the proteomic profile of meningioma. [244][245][246][247][248][249] The quantifiable proteome in meningioma seems to differ according to WHO grade, 239,248 sex 244 and intracranial location. 249 Highly abundant proteins in prognostically relevant molecular subgroups can help narrow down potential immunohistochemical markers, as few pathology laboratories perform proteomics for diagnostic purposes.…”

“…An upcoming ‘omic’ in meningioma research, closest to the resulting phenotype, is proteomics. To this date, few studies investigated the proteomic profile of meningioma 244–249 . The quantifiable proteome in meningioma seems to differ according to WHO grade, 239,248 sex 244 and intracranial location 249 .…”