Abstract
Objective Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein, which plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. However, little was known about the correlation between PTBP1 and glioma and its prognostic significance in glioma patients. Our aim was to investigate the expression, functional role, and prognostic value of PTBP1 in glioma. Methods We explored the expression of PTBP1 protein using immunohistochemistry in 150 adult malignant glioma tissues and 20 normal brain tissues and evaluated its association with clinicopathological parameters by chi-square test. Kaplan-Meier method was used to evaluate the prognostic effect of PTBP1 in glioma. Univariate/multivariate Cox analyses were used to identify independent prognostic factors. Transcriptional regulation network was constructed based on differentially expressed genes (DEGs) of PTBP1 from TCGA/CGGA database. GO and KEGG enrichment analyses were used to explore the function and pathways of DEGs. Results Out of the 150 malignant glioma tissues (60 LGG and 90 GBMs) and 20 normal brain tissues in our cohort, PTBP1 protein was high expressed in glioma tissues (79/150, 52.7%), but no expression was detected in normal brain tissues (0/20, 0%). The expression of PTBP1 was significantly higher in GBMs (P < 0.001). More than half of GBMs (62/90, 68.9%) were PTBP1 high expression. Chi-square test showed that the expression of PTBP1 was correlated with patient age, WHO grade, Ki-67 index, and IDH status. High expression of PTBP1 was significantly associated with poor prognosis in glioma, and it was an independent risk factor in glioma patients. Furthermore, we shed light on the underlying mechanism of PTBP1 by constructing a miR-218-TCF3-PTBP1 transcriptional network in glioma. Conclusion PTBP1 was high expressed in glioma, and it significantly correlated with poor prognosis, suggesting a potential therapeutic target for glioma, particularly for GBM.
Highlights
Gliomas are the most common primary intracranial neoplasms, categorized into grades 1 to 4 according to the World Health Organization (WHO) grading system
Polypyrimidine tract-binding protein 1 (PTBP1) protein was highly expressed in glioma tissues (79/150, 52.7%), but no expression was detected in normal brain tissues (0/20, 0%) in our cohort (Figure 1)
The high expression rate of PTBP1 increased with WHO grade (4/30, 13.3% in WHO 2; 13/30,43.3% in WHO 3; and 62/ 90, 68.9% in WHO 4)
Summary
Gliomas are the most common primary intracranial neoplasms, categorized into grades 1 to 4 according to the World Health Organization (WHO) grading system. Except for pilocytic astrocytoma (WHO grade 1, a borderline tumor with unique molecular profiles and an extremely good prognosis), all the WHO 2-4 gliomas are malignant tumors. They are the most lethal brain tumors with the high morbidity and mortality rates. Despite the basic research indepth and advances in surgical techniques over the past few years, the pathogenic mechanism of these malignant diseases remains unclear and the prognosis of them still has not been greatly improved. The researchers have discovered that there are approximately 145 genes involved in RNA splicing, which are widely expressed in brain, breast, colon, and prostate cancer [1]. Polypyrimidine tract binding protein (PTB) is a multifunctional component of mRNA metabolism that
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