Zhang Jingwen, Fu Minjie, Zhang Mengli, Zhang Jinsen, Du Zunguo, Zhang Hongyi, Hua Wei, Mao Ying
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Department of Ultrasound, Hebei General Hospital, Shijiazhuang, China.
Front Oncol. 2021 Jun 10;11:665360. doi: 10.3389/fonc.2021.665360. eCollection 2021.
, an interferon (IFN)-inducible gene, plays a promotional role in many tumors. However, its function in glioma remains unknown. In this study, bioinformatic analysis (TCGA, CGGA, Rembrandt) illustrated the upregulation and prognostic value of in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, < 0.0001). It also could be included in nomogram as a parameter to predict the 3- and 5-year survival risk (C-index = 0.86). The biological process of in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. expression had a positive association with most inflammatory-related functions, such as hematopoietic cell kinase (HCK) (R = 0.31), interferon (R = 0.72), STAT1 (R = 54), and a negative correlation with IgG (R = -0.24). Furthermore, expression tends to be positively related to multiple infiltrating immune cells, while negatively related to CD56 dim nature killer cell in glioma. Some important immune checkpoints, like , , , , and , were all positively related with (all Pearson correlation R > 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, < 0.0001) and GBM cells. These results indicated that might have important clinical significance in glioma and could serve as a potential immune therapeutic target.
DDX60是一种干扰素（IFN）诱导基因，在许多肿瘤中发挥促进作用。然而，其在胶质瘤中的功能仍不清楚。在本研究中，生物信息学分析（TCGA、CGGA、Rembrandt）表明DDX60在胶质瘤中上调且具有预后价值。对49例临床样本的免疫组织化学染色验证了胶质瘤中DDX60的表达高于正常组织（20例，P<0.0001）。它也可作为预测3年和5年生存风险的参数纳入列线图（C指数=0.86）。通过基因集富集分析（GSEA）和基因本体（GO）分析，DDX60在胶质瘤中的生物学过程主要富集于炎症和免疫反应。DDX60的表达与大多数炎症相关功能呈正相关，如造血细胞激酶（HCK）（R=0.31）、干扰素（R=0.72）、信号转导和转录激活因子1（STAT1）（R=0.54），与免疫球蛋白G（IgG）呈负相关（R=-0.24）。此外，在胶质瘤中，DDX60的表达倾向于与多种浸润性免疫细胞呈正相关，而与CD56dim自然杀伤细胞呈负相关。一些重要的免疫检查点，如CTLA4、PDCD1、PDCD1LG2、LAG3和HAVCR2，均与DDX60呈正相关（所有皮尔逊相关系数R>0.26）。临床样本（n=14，P<0.0001）和胶质母细胞瘤细胞中的蛋白质免疫印迹法证实了DDX60、表皮生长因子（EGF）和程序性死亡受体配体1（PD-L1）之间的表达及相关性。这些结果表明，DDX60在胶质瘤中可能具有重要的临床意义，并可作为潜在的免疫治疗靶点。
