Ma Kaiming, Chen Xin, Zhao Xiaofang, Chen Suhua, Yang Jun
Department of Neurosurgery, Peking University Third Hospital, Beijing, China.
Center for Precision Neurosurgery and Oncology of Peking University Health Science Center, Beijing, China.
Heliyon. 2022 Aug 19;8(8):e10298. doi: 10.1016/j.heliyon.2022.e10298. eCollection 2022 Aug.
Previous reports have confirmed the significance of plasmalemma vesicle-associated protein (PLVAP) in the progression of multiple tumors; however, there are few studies examining its immune properties in the context of gliomas. Here, we methodically investigated the pathophysiological characteristics and clinical manifestations of gliomas. A total of 699 patients diagnosed with gliomas in the cancer genome atlas along with 325 glioma patients in the Chinese glioma genome atlas were collected for the training and validation sets. We analyzed and visualized the total statistics using RStudio. PLVAP was markedly upregulated among high grade gliomas, O-methylguanine-DNA methyltransferase promoter unmethylated subforms, isocitrate dehydrogenase wild forms, 1p19q non-codeletion subforms, and mesenchyme type gliomas. The receiver operating characteristics analysis illustrated the favorable applicability of PLVAP in regard to estimating mesenchyme subform gliomas. Subsequent Kaplan-Meier curves together with multivariable Cox analyses upon survival identified high-expression PLVAP as a distinct prognostic variable for patients with gliomas. Gene ontology analysis of PLVAP among gliomas has documented the predominant role of this protein in glioma-associated immunobiological processes and also in inflammatory responses. We consequently examined the associations of PLVAP with immune-related meta-genes, and PLVAP was positively correlated with hematopoietic cell kinase, lymphocyte-specific protein tyrosine kinase, major histocompatibility complex (MHC) I, MHC II, signal transducer and activator of transcription 1, and interferon and was negatively correlated with immunoglobulin G. Moreover, association analyses between PLVAP and glioma-infiltrating immunocytes indicated that the infiltrating degrees of most immune cells exhibited positive correlations with PLVAP expression, particularly immunosuppressive subsets such as tumor-related macrophages, myeloid-derived suppressor cells, and regulatory T lymphocytes. In summary, we originally demonstrated that PLVAP is markedly associated with immunosuppressive immune cell infiltration degrees, unfavorable survival, and adverse pathology types among gliomas, thus identifying PLVAP as a practicable marker and a promising target for glioma-based precise diagnosis and therapeutic strategies.
先前的报告已经证实了质膜囊泡相关蛋白（PLVAP）在多种肿瘤进展中的重要性；然而，很少有研究在胶质瘤的背景下研究其免疫特性。在这里，我们系统地研究了胶质瘤的病理生理特征和临床表现。收集了癌症基因组图谱中699例诊断为胶质瘤的患者以及中国胶质瘤基因组图谱中的325例胶质瘤患者作为训练集和验证集。我们使用RStudio分析并可视化了总体统计数据。PLVAP在高级别胶质瘤、O-甲基鸟嘌呤-DNA甲基转移酶启动子未甲基化亚型、异柠檬酸脱氢酶野生型、1p19q非共缺失亚型和间充质型胶质瘤中显著上调。受试者工作特征分析表明PLVAP在评估间充质亚型胶质瘤方面具有良好的适用性。随后的Kaplan-Meier曲线以及生存的多变量Cox分析确定高表达PLVAP是胶质瘤患者的一个独特预后变量。对胶质瘤中PLVAP的基因本体分析记录了该蛋白在胶质瘤相关免疫生物学过程以及炎症反应中的主要作用。因此，我们研究了PLVAP与免疫相关元基因的关联，PLVAP与造血细胞激酶、淋巴细胞特异性蛋白酪氨酸激酶、主要组织相容性复合体（MHC）I、MHC II、信号转导和转录激活因子1以及干扰素呈正相关，与免疫球蛋白G呈负相关。此外，PLVAP与胶质瘤浸润免疫细胞之间的关联分析表明，大多数免疫细胞的浸润程度与PLVAP表达呈正相关，特别是免疫抑制亚群，如肿瘤相关巨噬细胞、骨髓来源的抑制细胞和调节性T淋巴细胞。总之，我们首次证明PLVAP与胶质瘤中免疫抑制性免疫细胞浸润程度、不良生存和不良病理类型显著相关，从而将PLVAP确定为基于胶质瘤的精确诊断和治疗策略的可行标志物和有前景的靶点。
