Du Shaonan, Guan Shu, Zhu Chen, Guo Qing, Cao Jingyuan, Guan Gefei, Cheng Wen, Cheng Peng, Wu Anhua
Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Department of Surgical Oncology and Breast Surgery, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Onco Targets Ther. 2020 Nov 18;13:11755-11768. doi: 10.2147/OTT.S275452. eCollection 2020.
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.
The least absolute shrinkage and selection operator (LASSO) regression was employed for establishing the SPKKPs signature for 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.
A SPKKPs classifier was constructed with 3 genes of this family. This signature could effectively distinguish 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.
These data indicate that the potential of FAM20C serving as a predictive molecule and a therapeutic target for GBM.
胶质母细胞瘤（GBM）是成人中枢神经系统中最致命的原发性癌症，迫切需要新的治疗策略。分泌途径激酶或激酶样蛋白（SPKKP）已被证明可通过磷酸化细胞外蛋白和蛋白聚糖来介导多种生理功能。然而，它们在癌症，尤其是GBM中的作用仍不清楚。
采用最小绝对收缩和选择算子（LASSO）回归建立野生型（wt）GBM预后的SPKKP特征。通过对多个数据集的综合分析来鉴定该基因家族在胶质瘤中的核心成员。分别使用受试者工作特征（ROC）曲线和免疫组织化学来评估其与胶质瘤恶性进展和GBM患者生存的相关性。基因集富集分析（GSEA）和京都基因与基因组百科全书（KEGG）用于解释其在GBM中的功能，并在体外进一步验证。
构建了一个由该家族3个基因组成的SPKKP分类器。该特征能够有效区分wt GBM的生存期。序列相似性家族20 C（FAM20C）被进一步鉴定为该家族在胶质瘤中的核心成员。FAM20C表达升高不仅与胶质瘤恶性进展和GBM的间充质亚型密切相关，还提示GBM患者预后不良。还发现FAM20C与GBM微环境中免疫反应的破坏有关，并且是胶质瘤和免疫细胞迁移所必需的。
这些数据表明FAM20C作为GBM的预测分子和治疗靶点的潜力。
