Abstract
ETS transcription factor ELK3 (ELK3), a novel oncogene, affects pathological processes and progression of many cancers in human tissues. However, it remains unclear whether ELK3, 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 ELK3 and the malignant progression of gliomas by analyzing clinical sample information stored in multiple databases. We revealed the putative mechanism of ELK3 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 ELK3 in gliomas was confirmed. Kaplan-Meier and Cox regression analyses demonstrated that a high ELK3 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 ELK3 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 ELK3 overexpression markedly promoted the proliferation and migration of glioma cells. Finally, gene set enrichment analysis (GSEA) and western blotting confirmed that overexpression of ELK3 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, ELK3 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.
Highlights
Gliomas, a special type of tumor derived from glial cells of the central nervous system, are the most common type of primary malignant cancer in the brain, accounting for approximately 81% of malignant brain tumors [1]
Based on the GEPIA database, we found that ELK3 is abnormally highly expressed in lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), acute myeloid leukemia (LAML), pancreatic adenocarcinoma (PAAD), skin cutaneous melanoma (SKCM), Stomach adenocarcinoma (STAD), testicular germ cell tumors (TGCT), thymoma (THYM), and other tumor tissues, including GBM and lower grade gliomas (LGG) (Figure 1A)
Analysis based on two datasets from the GEO database, GSE4290 and GSE50161, indicated that ELK3 expression was higher in gliomas than in normal brain tissues (Figures 1B, C)
Summary
A special type of tumor derived from glial cells of the central nervous system, are the most common type of primary malignant cancer in the brain, accounting for approximately 81% of malignant brain tumors [1]. Radiotherapy, and chemotherapy, patients with high-grade gliomas can attain delayed tumor progression, and these treatments prolong survival. High-grade gliomas exhibit invasive growth, high recurrence, and extremely complex pathological processes, and the average survival time of patients with gliomas is only 15 months due to the lack of specific biomarkers for diagnosis and individualized treatment [3, 4]. Tumor biomarkers can be used for screening, differential diagnosis, and clinical staging of cancer. They can be used to evaluate tumor volume and response to treatment as prognostic indicators of disease progression [5]. There is an urgent need for a highly specific and sensitive biomarker for gliomas identification, early diagnosis, and molecular-targeted therapy to prolong the survival of patients with gliomas
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
