原发性恶性脑肿瘤占所有脑肿瘤的三分之一以上，尽管通过分子研究来识别癌症驱动突变，但由于肿瘤内的高度异质性，目前可用的治疗方案仍具有挑战性。此外，免疫抑制和炎症性肿瘤微环境会加剧癌症的进展。因此，我们定义了脑膜瘤和神经胶质瘤的免疫和炎症分析，以阐明免疫浸润在这些癌症类型中的作用。使用 158 个脑肿瘤样本的组织微阵列，我们评估了 CD3、CD4、CD8、CD20、CD138、颗粒酶 B通过免疫组织化学 (IHC) 检测 (GzmB)、5-脂氧合酶 (5-LOX)、程序性死亡配体 1 (PD-L1)、O-6-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 和转谷氨酰胺酶 2 (TG2) 的表达。 IHC 结果使用 Spearman 相关矩阵进行关联。使用 GEPIA2 上胶质母细胞瘤 (GBM) 和低级别胶质瘤 (LGG) 队列中可用的公共数据集评估转录表达、相关性和总生存 (OS) 分析。十分之七的标记物在至少一种中显示出显着不同的 IHC 表达在评估的队列中，CD3、CD4 和 5-LOX 在 GBM 和星形细胞瘤之间表达存在差异。相关矩阵分析显示，5-LOX 和 GzmB 表达在脑膜瘤和 GBM 中均相关，而 5-LOX 表达在脑膜瘤和星形细胞瘤队列中均与 TG2 显着正相关。这些发现通过 TCGA-GBM 和 LGG 数据集的相关分析得到证实。 mRNA 水平分析表明，与对照组织相比，GBM 中 CD3（CD3D、CD3E）和 CD138（SDC1）表达显着增加。在 GBM 和 LGG 中，肿瘤样本中的 CD4 和 5-LOX (ALOX5) mRNA 水平明显高于正常组织。在 GBM 队列中，GzmB (GZMB)、SDC1 和 MGMT 基因表达预测总生存期 (OS) 较差。此外，在 LGG 队列中，CD3（CD3D、CD3E、CD3G）、CD8（CD8A）、GZMB、CD20（MS4A1）、SDC1、PD-L1、ALOX5 和 TG2（TGM2）基因表达增加与较差的 OS 相关我们的数据显示，5-LOX 和 GzmB 的表达在 RNA 和蛋白质水平上均存在显着的正相关性。需要进一步评估以了解 5-LOX 和免疫浸润在神经胶质瘤进展中的相互作用。© 2024。作者。

Primary malignant brain tumours are more than one-third of all brain tumours and despite the molecular investigation to identify cancer driver mutations, the current therapeutic options available are challenging due to high intratumour heterogeneity. In addition, an immunosuppressive and inflammatory tumour microenvironment strengthens cancer progression. Therefore, we defined an immune and inflammatory profiling of meningioma and glial tumours to elucidate the role of the immune infiltration in these cancer types.Using tissue microarrays of 158 brain tumour samples, we assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1 (PD-L1), O-6-Methylguanine-DNA Methyltransferase (MGMT) and Transglutaminase 2 (TG2) expression by immunohistochemistry (IHC). IHC results were correlated using a Spearman correlation matrix. Transcript expression, correlation, and overall survival (OS) analyses were evaluated using public datasets available on GEPIA2 in Glioblastoma (GBM) and Lower Grade Glioma (LGG) cohorts.Seven out of ten markers showed a significantly different IHC expression in at least one of the evaluated cohorts whereas CD3, CD4 and 5-LOX were differentially expressed between GBMs and astrocytomas. Correlation matrix analysis revealed that 5-LOX and GzmB expression were associated in both meningiomas and GBMs, whereas 5-LOX expression was significantly and positively correlated to TG2 in both meningioma and astrocytoma cohorts. These findings were confirmed with the correlation analysis of TCGA-GBM and LGG datasets. Profiling of mRNA levels indicated a significant increase in CD3 (CD3D, CD3E), and CD138 (SDC1) expression in GBM compared to control tissues. CD4 and 5-LOX (ALOX5) mRNA levels were significantly more expressed in tumour samples than in normal tissues in both GBM and LGG. In GBM cohort, GzmB (GZMB), SDC1 and MGMT gene expression predicted a poor overall survival (OS). Moreover, in LGG cohort, an increased expression of CD3 (CD3D, CD3E, CD3G), CD8 (CD8A), GZMB, CD20 (MS4A1), SDC1, PD-L1, ALOX5, and TG2 (TGM2) genes was associated with worse OS.Our data have revealed that there is a positive and significant correlation between the expression of 5-LOX and GzmB, both at RNA and protein level. Further evaluation is needed to understand the interplay of 5-LOX and immune infiltration in glioma progression.© 2024. The Author(s).