Yang Ying, Wang Jin, Xu Shihai, Shi Fei, Shan Aijun
Department of Pediatrics, Futian Women and Children Health Institute, Shenzhen 518045, China.
Department of Emergency, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
Transl Neurosci. 2021 Feb 3;12(1):67-75. doi: 10.1515/tnsci-2021-0004. eCollection 2021 Jan 1.
Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear.
Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses.
CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including -cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age.
CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.
据报道，钙网蛋白（CALU）在某些恶性肿瘤中与侵袭性和转移相关。然而，在胶质瘤中，CALU的作用仍不清楚。
纳入998例胶质瘤患者的临床和转录组数据，其中301例来自CGGA数据集，697例来自TCGA数据集。使用R语言进行统计分析。
CALU表达在更恶性的胶质瘤中显著上调，包括更高分级、异柠檬酸脱氢酶（IDH）野生型、间充质和经典亚型。基因本体分析显示，与CALU相关的基因主要富集在细胞/生物粘附、伤口反应和细胞外基质/结构组织中，所有这些都与上皮-间质转化（EMT）表型密切相关。基因集富集分析（GSEA）进一步证实了CALU在EMT中的深度参与。随后的基因集变异分析（GSVA）表明，CALU与三种EMT信号通路特别相关，包括转化生长因子β（TGFβ）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）和缺氧通路。此外，CALU与EMT关键标志物协同发挥作用，包括E-钙粘蛋白、波形蛋白、蜗牛蛋白、蛞蝓蛋白和TWIST1。生存和Cox回归分析表明，较高的CALU预示着较差的生存率，且预后价值独立于世界卫生组织（WHO）分级和年龄。
CALU与胶质瘤中更恶性的表型相关。此外，CALU似乎作为一种促进EMT的分子靶点，并且可以独立地有助于预测胶质瘤的预后。
