AUTHOR=Zhang Jingwen , Fu Minjie , Zhang Mengli , Zhang Jinsen , Du Zunguo , Zhang Hongyi , Hua Wei , Mao Ying 

TITLE=DDX60 Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.665360

DOI=10.3389/fonc.2021.665360

ISSN=2234-943X

ABSTRACT=<p><italic>DDX60</italic>, 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 <italic>DDX60</italic> in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, <italic>P</italic> &lt; 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 <italic>DDX60</italic> in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. <italic>DDX60</italic> 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, <italic>DDX60</italic> 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 <italic>CTLA-4</italic>, <italic>PD-L1</italic>, <italic>EGF</italic>, <italic>CD96</italic>, and <italic>CD226</italic>, were all positively related with <italic>DDX60</italic> (all Pearson correlation R &gt; 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, <italic>P</italic> &lt; 0.0001) and GBM cells. These results indicated that <italic>DDX60</italic> might have important clinical significance in glioma and could serve as a potential immune therapeutic target.</p>