AUTHOR=Liu Zhendong , Ren Zhishuai , Zhang Cheng , Qian Rongjun , Wang Hongbo , Wang Jialin , Zhang Wang , Liu Binfeng , Lian Xiaoyu , Wang Yanbiao , Guo Yuqi , Gao Yanzheng 

TITLE=ELK3: A New Molecular Marker for the Diagnosis and Prognosis of Glioma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.608748

DOI=10.3389/fonc.2021.608748

ISSN=2234-943X

ABSTRACT=<p>ETS transcription factor ELK3 <italic>(ELK3)</italic>, a novel oncogene, affects pathological processes and progression of many cancers in human tissues. However, it remains unclear whether <italic>ELK3</italic>, as a key gene, affects the pathological process of gliomas and the prognosis of patients with gliomas. This study aimed to comprehensively and systematically reveal the correlation between <italic>ELK3</italic> and the malignant progression of gliomas by analyzing clinical sample information stored in multiple databases. We revealed the putative mechanism of <italic>ELK3</italic> involvement in malignant gliomas progression and identified a new and efficient biomarker for glioma diagnosis and targeted therapy. Based on the sample data from multiple databases and real-time quantitative polymerase chain reaction (RT-qPCR), the abnormally high expression of <italic>ELK3</italic> in gliomas was confirmed. Kaplan-Meier and Cox regression analyses demonstrated that a high <italic>ELK3</italic> expression was markedly associated with low patient survival and served as an independent biomarker of gliomas. Wilcox and Kruskal-Wallis tests revealed that expression of <italic>ELK3</italic> was positively correlated with several clinical characteristics of patients with gliomas, such as age, WHO classification, and recurrence. Moreover, Cell Counting Kit‐8 (CCK-8), immunofluorescence, and wound healing assays confirmed that <italic>ELK3</italic> overexpression markedly promoted the proliferation and migration of glioma cells. Finally, gene set enrichment analysis (GSEA) and western blotting confirmed that overexpression of <italic>ELK3</italic> regulated the JAK–STAT signaling pathway and upregulate the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (P-STAT3) to promote the malignant transition of gliomas. Therefore, <italic>ELK3</italic> may serve as an efficient biomarker for the diagnosis and prognosis of gliomas and it can also be used as a therapeutic target to improve the poor prognosis of patients with gliomas.</p>