Department of Neurosurgery, Xiang-Ya Hospital, Central South University, Changsha, China.
Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China.
Cell Death Dis. 2021 Mar 12;12(3):261. doi: 10.1038/s41419-021-03547-5.
In order to set up a reliable prediction system for the tumor grade and prognosis in glioma patients, we clarify the complicated crosstalk of Annexin A2 (ANXA2) with Glypican 1 (GPC1) and demonstrate whether combined indexes of ANXA2 and GPC1 could improve the prognostic evaluation for glioma patients. We found that ANXA2-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of GPC1 via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which eventually led to enhanced proliferation of glioma cells. Both mRNA and protein levels of ANXA2 were upregulated in glioma tissues and coincided with the overexpression of GPC1. Besides, we utilized tissue microarrays (TMAs) and immunohistochemistry to demonstrate that glioma patients with both high expression of ANXA2 and GPC1 tended to have higher rate of tumor recurrence and shorter overall survival (OS). In conclusion, the overexpression of ANXA2 promotes proliferation of glioma cells by forming a GPC1/c-Myc positive feedback loop, and ANXA2 together with its downstream target GPC1 could be a potential "combination biomarker" for predicting prognosis of glioma patients.
为了建立一个可靠的胶质瘤患者肿瘤分级和预后预测系统，我们阐明了膜联蛋白 A2（ANXA2）与聚糖蛋白 1（GPC1）之间复杂的串扰，并证明 ANXA2 和 GPC1 的联合指标是否可以改善对胶质瘤患者的预后评估。我们发现 ANXA2 以 c-Myc 依赖的方式诱导神经胶质瘤细胞增殖。ANXA2 通过 c-Myc 增加 GPC1 的表达，而上调的 GPC1 进一步促进 c-Myc 水平，形成正反馈环，最终导致神经胶质瘤细胞增殖增强。ANXA2 的 mRNA 和蛋白水平在胶质瘤组织中上调，与 GPC1 的过表达一致。此外，我们利用组织微阵列（TMA）和免疫组织化学证实，同时高表达 ANXA2 和 GPC1 的胶质瘤患者具有更高的肿瘤复发率和更短的总生存期（OS）。总之，ANXA2 的过表达通过形成 GPC1/c-Myc 正反馈环促进神经胶质瘤细胞的增殖，并且 ANXA2 与其下游靶标 GPC1 可能是预测神经胶质瘤患者预后的潜在“组合生物标志物”。
