Abstract
Pleomorphic adenoma gene like-2 (PLAGL2) has been implicated in the development and progression of diverse malignancies, including glioblastoma. An increasing number of studies have reported that dysregulated expression of PLAGL2 is a common phenomenon in different malignancies. However, the mechanism and biological functions of PLAGL2 in patients with high-grade glioma (HGG) remain unclear. In addition, the expression and clinical significance of PLAGL2 in HGG have not yet been reported. Herein, we investigated the expression patterns and prognostic values of PLAGL2 in patients with HGG by using various databases, including Tumor Immune Estimation Resource 2.0 (TIMER2.0), GENT2, ONCOMINE, GEPIA, Human Protein Atlas, and Gene Expression Omnibus datasets. In the present study, we analyzed the relationship between PLAGL2 mRNA expression and clinical parameters in 184 HGG cases and found that PLAGL2 presented positively high expression and was relevant to poor prognosis. Immunohistochemistry analysis confirmed the overexpression of PLAGL2 protein, which is mainly expressed in the nucleus of glioma. Additionally, a high level of expression of the PLAGL2 gene was associated with lower survival in progression-free survival and overall survival in GBM patients. The correlation analysis between PLAGL2 and immune infiltration related to the abundance of B cells, CD8+ T cells, CD4+ T cells, macrophages, DCs, and neutrophils was also performed using TIMER2.0. GSEA results showed that high PLAGL2 expression was associated with cell migration, proliferation, actin cytoskeletal, and angiogenesis. To sum up, our findings indicated that PLAGL2 could serve as an independent prognostic biomarker and might be a potential therapeutic target for HGG, which should be further investigated.
Highlights
Malignant gliomas, encompassing a heterogeneous cluster of subtypes, are the most common primary central nervous system (CNS) tumors in both children and adults
According to Timer analysis, Pleomorphic adenoma gene like-2 (PLAGL2) was upregulated in bladder, breast, cervix, bile ducts, colorectal, esophagus, kidney, liver, lung, stomach, and CNS cancer compared with normal cases (Figure 1A, Supplementary Table S1), whereas it was downregulated in renal and thyroid cancers
The results showed that PLAGL2 was upregulated in several cancers, including adrenal gland, brain, breast, cervix, colon, esophagus, liver, lung, oral, ovary, and skin
Summary
Malignant gliomas, encompassing a heterogeneous cluster of subtypes, are the most common primary central nervous system (CNS) tumors in both children and adults. Glioma is considered one of the deadliest cancers worldwide, with the incidence at 5/100,000 each year (Dunn et al, 2012; Hu et al, 2016). While low-grade gliomas (LGGs) are often treated with surgery, radiotherapy, and chemotherapy, high-grade gliomas (HGGs) are aggressive and virtually incurable. An HGG, especially in its most aggressive form (glioblastoma), has an average survival of 1 year and often presents with progressive neurologic signs and symptoms characterized by radiochemotherapy resistance (Furnari et al, 2007; Taylor and Gerstner, 2013). Grade III astrocytoma and grade IV glioblastoma multiforme (GBM) are the most severe and incurable forms with dismal prognoses (Giese et al, 2003; Wen and Kesari, 2008). Screening for new molecular biomarkers is crucial for improving prognosis and creating an individualized treatment for glioma
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
