Zhang Huikai, Xu Yang, Deng Gang, Yuan Fanen, Tan Yinqiu, Gao Lun, Sun Qian, Qi Yangzhi, Yang Kun, Geng Rongxin, Jiang Hongxiang, Liu Baohui, Chen Qianxue
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
J Cancer. 2021 Mar 10;12(9):2756-2767. doi: 10.7150/jca.48419. eCollection 2021.
Serum amyloid A1 (SAA1) is an inflammatory associated high-density lipoprotein. And It is also considered as a predictor and prognostic marker of cancer risk. However, its role and mechanisms in glioblastoma (GBM) still unclear. In this study, we validate that SAA1 is up-regulated in GBM, and its high expression predicts poor prognosis. SAA1 knockdown promotes the apoptosis of GBM cell. Mechanistically, SAA1 knockdown can inhibit serine/threonine protein kinase B (AKT) phosphorylation, thereby regulating the expression of apoptosis-related proteins such as Bcl2 and Bax, leading to GBM cell death. Moreover, Gliomas with low SAA1 expression have increased sensitivity to Temozolomide (TMZ). Low SAA1 expression segregated glioma patients who were treated with Temozolomide (TMZ) or with high MGMT promoter methylation into survival groups in TCGA and CGGA dataset. Our study strongly suggested that SAA1 was a regulator of cells apoptosis and acted not only as a prognostic marker but also a novel biomarker of sensitivity of glioma to TMZ.
血清淀粉样蛋白A1(SAA1)是一种与炎症相关的高密度脂蛋白。它也被视为癌症风险的预测指标和预后标志物。然而,其在胶质母细胞瘤(GBM)中的作用及机制仍不清楚。在本研究中,我们证实SAA1在GBM中上调,其高表达预示预后不良。敲低SAA1可促进GBM细胞凋亡。机制上,敲低SAA1可抑制丝氨酸/苏氨酸蛋白激酶B(AKT)磷酸化,从而调节凋亡相关蛋白如Bcl2和Bax的表达,导致GBM细胞死亡。此外,SAA1表达低的胶质瘤对替莫唑胺(TMZ)的敏感性增加。在TCGA和CGGA数据集中,SAA1低表达将接受替莫唑胺(TMZ)治疗或具有高甲基化MGMT启动子的胶质瘤患者分为不同的生存组。我们的研究强烈表明,SAA1是细胞凋亡的调节因子,不仅作为预后标志物,而且是胶质瘤对TMZ敏感性的新型生物标志物。