Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas.

Astrocytic tumors are known for their high progression capacity and high mortality rates; in this regard, proteins correlated to prognosis can aid medical conduct. Although several genetic changes related to progression from grade 2 to grade 4 astrocytoma are already known, mRNA copies do not necessarily correlate with protein abundance and therefore could shadow further comprehension about this tumor's biology. This motivates us to seek for complementary strategies to study tumor progression at the protein level. Here we compare the proteomic profile of biopsies from patients with grade 2 (diffuse, n = 6) versus grade 4 astrocytomas (glioblastomas, n = 10) using shotgun proteomics. Data analysis performed with PatternLab for proteomics identified 5,206 and 6,004 proteins in the 2- and 4-grade groups, respectively. Our results revealed seventy-four differentially abundant proteins (p < 0.01); we then shortlist those related to greater malignancy. We also describe molecular pathways distinctly activated in the two groups, such as differences in the organization of the extracellular matrix, decisive both in tumor invasiveness and in signaling for cell division, which, together with marked contrasts in energy metabolism, are determining factors in the speed of growth and dissemination of these neoplasms. The degradation pathways of GABA, enriched in the grade 2 group, is consistent with a favorable prognosis. Other functions such as platelet degranulation, apoptosis, and activation of the MAPK pathway were correlated to grade 4 tumors and, consequently, unfavorable prognoses. Our results provide an important survey of molecular pathways involved in glioma pathogenesis for these histopathological groups.

Microsurgical Resection of Petroclival Meningioma via the Posterior Petrosal Approach: Three-Dimensional Operative Video.

Petroclival meningiomas are complex, deep-seated lesions related to many critical neurovascular structures. We present the case of a 44-year-old woman who had presented with a history of severe facial pain, hearing loss, and tinnitus on the left side, associated with left facial hypoesthesia (Video 1). Preoperative magnetic resonance imaging demonstrated a mass highly suggestive of a left petroclival meningioma. Considering the worsening symptoms and important mass effect, microsurgical resection using the posterior petrosal approach was performed. Mastoidectomy was performed first, followed by craniotomy encompassing both posterior and middle cranial fossae. The posterior fossa and middle fossa dural incisions were connected, coagulating and sectioning the superior petrosal sinus. Next, the tentorium was cut all the way toward the incisura, with care to preserve the fourth nerve in the last cut. After completion of the tentorium incision, the presigmoid space increased. The lesion was totally resected using microsurgical techniques, with the aid of an ultrasonic aspirator to debulk the mass and allow for its circumferential dissection. Postoperative magnetic resonance imaging demonstrated complete tumor resection. The patient presented with improvement of symptoms and no new neurological deficit during follow-up. Skull base approaches, such as the posterior petrosal approach, are useful for successfully treating challenging lesions such as the one presented, with low morbidity. Laboratory training is essential to be familiarized with the complex intraoperative neuroanatomical nuances. The patient provided written informed consent for the report of her case and operative video. The anatomical images were provided courtesy of the Rhoton Collection, American Association of Neurological Surgeons/Neurosurgical Research and Education Foundation.

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

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.