OncoTargets and Therapy (Nov 2020)
Secretory Pathway Kinase FAM20C, a Marker for Glioma Invasion and Malignancy, Predicts Poor Prognosis of Glioma
Abstract
Shaonan Du,1 Shu Guan,2 Chen Zhu,1 Qing Guo,1 Jingyuan Cao,1 Gefei Guan,1 Wen Cheng,1 Peng Cheng,1 Anhua Wu1,3 1Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Surgical Oncology and Breast Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 3College of Applied Technology, China Medical University, Shenyang, Liaoning 110122, People’s Republic of ChinaCorrespondence: Anhua Wu; Peng ChengThe First Hospital of China Medical University, No. 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, People’s Republic of ChinaEmail [email protected]; [email protected]: 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.Keywords: glioblastoma, FAM20C, migration, invasion, prognosis
