Prognostic Significance of mRNA Expression RBBP8 or Its Methylation in Gliomas.

Zhendong Liu,Rongjun Qian,Zheyu Luan,Xingbo Cheng,Shaochong Lin,Wenjia Liang,Yanzheng Gao,Haoran Jin,Zhibin Han,Pengxu Li

doi:10.1007/s10571-022-01198-4

Abstract

Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan-Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 was remarkably enriched in cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.

Highlights

Glioma is the most common primary intracranial tumor in adults and is characterized by high heterogeneity, recurrence rates, and mortality (Guan et al 2018; Hu et al 2021)
Results of the reverse transcription-polymerase chain reaction (RT-PCR) showed that the mRNA expression level of Retinoblastoma-binding protein 8 (RBBP8) in the glioma cell line, A172, was significantly higher than that in the human astrocyte cell line (Fig. 1a)
We investigated RBBP8 expression levels in 33 common tumor types and found that aberrantly high expression of RBBP8 was common in tumors such as cervical squamous cell carcinoma, endocervical adenocarcinoma, lymphoid neoplasm diffuse large B-cell lymphoma, and lung squamous cell carcinoma (Fig. S1)

Summary

Introduction

Glioma is the most common primary intracranial tumor in adults and is characterized by high heterogeneity, recurrence rates, and mortality (Guan et al 2018; Hu et al 2021). Surgical resection is the main treatment for gliomas, regardless of its grade. Radiotherapy, and temozolomide chemotherapy, the prognosis of glioma patients remains unsatisfactory, especially in glioblastoma multiforme (GBM), which is the most common type of glioma (Reni et al 2017). The median survival time of GBM patients is less than two years after standard treatment (Gusyatiner and Hegi 2018). Some new treatments have been used in clinical trials, their effects are not satisfactory. More studies are needed to determine the prognosis of glioma patients and to develop new therapeutic targets

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Discussion

Conclusion