Cytoskeletal Protein Palladin in Adult Gliomas Predicts Disease Incidence, Progression, and Prognosis

SIMPLE SUMMARY: Glioma is a tumor originating from cells supporting the brain and represents a major health challenge. Palladin is a structural protein widely expressed in mammalian tissues and has a pivotal role in cytoskeletal dynamics in health and disease. Palladin is linked to the progression of breast, pancreatic, and renal cancers. However, the role of palladin in gliomas is yet unknown. In this work, we aimed to shed light on palladin’s role in glioma tumors using publicly available data, along with samples obtained from humans and mice. Our findings indicate that palladin expression might be linked to adult glioma progression and is associated with a worse prognosis. Overall, our results introduce the possibility of using palladin as a diagnostic and prognostic marker, as well as a potential future therapeutic target. ABSTRACT: Brain tumors comprise over 100 types of masses, differing in the following: location; patient age; molecular, histological, and immunohistochemical characteristics; and prognosis and treatment. Glioma tumors originate from neuroglia, cells supporting the brain. Palladin, a structural protein widely expressed in mammalian tissues, has a pivotal role in cytoskeletal dynamics and motility in health and disease. Palladin is linked to the progression of breast, pancreatic, and renal cancers. In the central nervous system, palladin is involved in embryonic development, neuronal maturation, the cell cycle, differentiation, and apoptosis. However, the role of palladin in brain tumors is unknown. In this work, we explored palladin’s role in glioma. We analyzed clinical data, along with bulk and single-cell gene expression. We then validated our results using IHC staining of tumor samples, together with qRT-PCR of glioma cell lines. We determined that wild-type palladin-4 is overexpressed in adult gliomas and is correlated with a decrease in survival. Palladin expression outperformed clinically used prognostic markers and was most prominent in glioblastoma. Finally, we showed that palladin originates from the malignant cell population. Our findings indicate that palladin expression might be linked to adult glioma progression and is associated with prognosis.