Dataset Information

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

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.

SUBMITTER: Mayer O

PROVIDER: S-EPMC9600953 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Mayer Ori O Bugis Joshua J Kozlova Daria D Leemann Aviv A Mansur Shahar S Peerutin Ilan I Mendelovich Noga N Mazin Meital M Friedmann-Morvinski Dinorah D Shomron Noam N

Cancers 20221019 20

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 c ...[more]

PMID: 36291914

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Project description:BackgroundRecently, increasing evidence has indicated that platelet-activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) plays an important role in several cancers. However, its role in lung adenocarcinoma (LUAD) has not been reported until now.MethodsThe expression of PAFAH1B3 in LUAD was determined by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and real-time PCR (RT-PCR), western blot and immunohistochemical (IHC) analyses. A chi-square test was used to investigate the correlation between PAFAH1B3 expression and clinical parameters. Cox regression and Kaplan-Meier analysis were performed to analyze the prognostic value of PAFAH1B3. The CCK-8 assay, clone formation assay, transwell invasion assay and flow cytometry were conducted to detect cell proliferation, clone formation, invasion and the cell cycle. The xenograft tumor model was constructed to explore the function of PAFAH1B3 in vivo. Western blot and IHC analyses were performed to detect epithelial-to-mesenchymal transition (EMT)-related markers. Immune Cell Abundance Identifier (ImmuneCellAI) and IHC analyses were used to analyze the effect of PAFAH1B3 on immune cell infiltration.ResultsOur study showed that the expression of PAFAH1B3 was upregulated in LUAD tissues and cells compared with noncancerous tissues and cells. Additionally, the results indicated that the expression of PAFAH1B3 was positively correlated with distant metastasis, TNM stage and poor clinical outcome and it was an independent prognostic risk factor for LUAD. In addition, silencing PAFAH1B3 suppressed cell proliferation, colony formation, and invasion and increased the cell population in the G0-G1 phases in vitro. Furthermore, our results showed that knockdown of PAFAH1B3 increased the epithelial marker E-cadherin level and decreased the mesenchymal marker N-cadherin level in vitro and in vivo. We also proved that PAFAH1B3 downregulation inhibited tumorigenesis and neutrophil infiltration in the xenograft tumor model.ConclusionOur studies indicate that PAFAH1B3, a prognostic risk factor, promotes proliferation, invasion and EMT and affects immune infiltrates in LUAD.

Project description:BackgroundGlioma is the most common primary brain tumor in adults and accounts for more than 70% of brain malignancies. Lipids are crucial components of biological membranes and other structures in cells. Accumulating evidence has supported the role of lipid metabolism in reshaping the tumor immune microenvironment (TME). However, the relationship between the immune TME of glioma and lipid metabolism remain poorly described.Materials and methodsThe RNA-seq data and clinicopathological information of primary glioma patients were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). An independent RNA-seq dataset from the West China Hospital (WCH) also included in the study. Univariate Cox regression and LASSO Cox regression model was first to determine the prognostic gene signature from lipid metabolism-related genes (LMRGs). Then a risk score named LMRGs-related risk score (LRS) was established and patients were stratified into high and low risk groups according to LRS. The prognostic value of the LRS was further demonstrated by construction of a glioma risk nomogram. ESTIMATE and CIBERSORTx were used to depicted the TME immune landscape. Tumor Immune Dysfunction and Exclusion (TIDE) was utilized to predict the therapeutic response of immune checkpoint blockades (ICB) among glioma patients.ResultsA total of 144 LMRGs were differentially expressed between gliomas and brain tissue. Finally, 11 prognostic LMRGs were included in the construction of LRS. The LRS was demonstrated to be an independent prognostic predictor for glioma patients, and a nomogram consisting of the LRS, IDH mutational status, WHO grade, and radiotherapy showed a C-index of 0.852. LRS values were significantly associated with stromal score, immune score, and ESTIMATE score. CIBERSORTx indicated remarkable differences in the abundance of TME immune cells between patients with high and low LRS risk levels. Based on the results of TIDE algorithm, we speculated that the high-risk group had a greater chance of benefiting from immunotherapy.ConclusionThe risk model based upon LMRGs could effectively predict prognosis in patients with glioma. Risk score also divided glioma patients into different groups with distinct TME immune characteristics. Immunotherapy is potentially beneficial to glioma patients with certain lipid metabolism profiles.

Dataset Information

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

Publications

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

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