Dataset Information

Secretory Pathway Kinase FAM20C, a Marker for Glioma Invasion and Malignancy, Predicts Poor Prognosis of Glioma.

ABSTRACT: Purpose:Glioblastoma (GBM) is the most lethal primary cancer in adult central nervous system, and new strategies are desperately needed. The secretory pathway kinase or kinase-like proteins (SPKKPs) have been shown to mediate multiple physiological functions by phosphorylating extracellular proteins and proteoglycans. However, their roles in cancers, especially GBM, remain poorly defined. Methods:The least absolute shrinkage and selection operator (LASSO) regression was employed for establishing the SPKKPs signature for IDH wild type (wt) GBM prognosis. Integrative analyses with multiple datasets were employed to identify the core member of this gene family in glioma. The receiver operator characteristic (ROC) curves and immunohistochemistry were further used for evaluating its association with progressive malignancy in glioma and GBM patients' survival, respectively. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to interpret its functions in GBM, which were further verified in vitro. Results:A SPKKPs classifier was constructed with 3 genes of this family. This signature could effectively distinguish IDH wt GBM survival. Family with sequence similarity 20 C (FAM20C) was further identified as the core member of this family in glioma. Elevated FAM20C expression was not only closely correlated with glioma malignancy progression and the mesenchymal subtype of GBM but also indicated unfavorable survival of GBM patients. FAM20C was also found to be associated with the disrupted immune response in GBM microenvironment and was required for the migration of glioma and immune cells. Conclusion:These data indicate that the potential of FAM20C serving as a predictive molecule and a therapeutic target for GBM.

SUBMITTER: Du S

PROVIDER: S-EPMC7680683 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Secretory Pathway Kinase <i>FAM20C</i>, a Marker for Glioma Invasion and Malignancy, Predicts Poor Prognosis of Glioma.

Du Shaonan S Guan Shu S Zhu Chen C Guo Qing Q Cao Jingyuan J Guan Gefei G Cheng Wen W Cheng Peng P Wu Anhua A

OncoTargets and therapy 20201118

<h4>Purpose</h4>Glioblastoma (GBM) is the most lethal primary cancer in adult central nervous system, and new strategies are desperately needed. The secretory pathway kinase or kinase-like proteins (SPKKPs) have been shown to mediate multiple physiological functions by phosphorylating extracellular proteins and proteoglycans. However, their roles in cancers, especially GBM, remain poorly defined.<h4>Methods</h4>The least absolute shrinkage and selection operator (LASSO) regression was employed f ...[more]

PMID: 33239887

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Project description:Studies have indicated that collagen α-1 (IV) chain (COL4A1) has an indispensable regulatory role in the complex pathological mechanisms of numerous types of malignant tumor. However, its role in the development of glioma has remained elusive. Therefore, the present study sought to determine the association between the expression levels of COL4A1 and the clinical characteristics of gliomas by analyzing large samples. First, analysis of thousands of glioma tissue samples collected from the Gene expression profiling interactive analysis, Gene Expression Omnibus database, the Ivy glioblastoma atlas, The Human Protein Atlas, Chinese Glioma Genome Atlas and The Cancer Genome Atlas. In addition, glioma tissues and normal brain tissues from patients with glioma and epilepsy undergoing surgical resection were collected. These samples, which were subjected to a variety of different detection techniques (including sequencing data, chip data, reverse transcription-quantitative PCR, cell lines and tissue samples, in situ hybridization and immunology) revealed that COL4A1 expression was not only increased at the mRNA level but also at the protein level as compared with that in normal brain tissue. Furthermore, Kaplan-Meier analysis revealed that COL4A1 expression was associated with reduced overall survival of patients, particularly those with World Health Organization grade III glioma. Receiver operating characteristic analysis suggested that COL4A1 had a moderate diagnostic value for glioma. In addition, the Mann-Whitney U-test or Kruskal-Wallis test indicated that the expression levels of COL4A1 were positively associated with the histological type and historical grade of the tumor, patient age, 'Primary, Recurrent, Secondary' type and the chemotherapy status, and negatively associated with isocitrate dehydrogenase mutation and 1p19q co-deletion (P<0.001). Gene-set enrichment analysis indicated that overexpression of COL4A1 promoted cancer-associated pathways, such as the JAK/STAT signaling pathway and cell cycle regulation. Finally, an MTT assay, immunohistochemical analysis of the cell cycle regulator KI67 and a wound-healing assay further confirmed that knockdown of COL4A1 inhibited the proliferation and migration ability of glioma cells. In conclusion, COL4A1, as a novel oncogene, is a marker for poor prognosis in patients with glioma. The present study expanded the understanding of the pathogenesis of glioma and identified COL4A1 as a potential target for the diagnosis and treatment of gliomas.

Dataset Information

Secretory Pathway Kinase FAM20C, a Marker for Glioma Invasion and Malignancy, Predicts Poor Prognosis of Glioma.

Publications

Secretory Pathway Kinase <i>FAM20C</i>, a Marker for Glioma Invasion and Malignancy, Predicts Poor Prognosis of Glioma.

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