Functions of RNF Family in the Tumor Microenvironment and Drugs Prediction in Grade II/III Gliomas.

Jingwei Zhang,Xisong Liang,Kui Yang,Fangkun Liu,Ziyu Dai,Quan Cheng,Xun Zhang,Zeyu Wang,Hao Zhang,Zhixiong Liu,Shuwang Li

doi:10.3389/fcell.2021.754873

Abstract

Increasing evidence has demonstrated that RING finger (RNF) proteins played a vital role in cellular and physiological processes and various diseases. However, the function of RNF proteins in low-grade glioma (LGG) remains unknown. In this study, 138 RNF family members revealed their role in LGG. The TCGA database was used as the training cohort; two CGGA databases and GSE108474 were selected as external validation cohorts. Patients were grouped into cluster 1 and cluster 2, both in the training and validation cohorts, using consensus clustering analysis. The prognosis of patients in cluster 1 is significantly better than that in cluster 2. Meanwhile, biofunction prediction was further introduced to explore the potential mechanisms that led to differences in survival outcomes. Patients in Cluster 2 showed more complicated immunocytes infiltration and highly immunosuppressive features than cluster 1. Enrichment pathways such as negative regulation of mast cell activation, DNA replication, mismatch repair, Th17 cell differentiation, antigen processing and presentation, dendritic cell antigen processing and presentation, dendritic cell differentiation were also enriched in cluster 2 patients. For the last, the main contributors were distinguished by employing a machine learning algorithm. A lot of targeted and small molecule drugs that are sensitive to patients in cluster 2 were predicted. Importantly, we discovered TRIM8, DTX2, and TRAF5 as the most vital contributors from the RNF family, which were related to immune infiltration in LGG tumor immune landscape. In this study, we demonstrated the predicted role of RNF proteins in LGG. In addition, we found out three markers among RNF proteins that are closely related to the immune aspects of LGG, which might serve as novel therapeutic targets for immunotherapy in the future.

Highlights

Diffuse gliomas, including low-grade glioma (LGG) and glioblastomas (GBM), are the most common malignant tumors among adults in the central nervous system (CNS) (Miller et al, 2019)
Low-grade glioma is a group of heterogeneous neoplasms originating from the glial cells nearby neurons and accounts for more than 6% of all primary central nervous system (CNS) tumors in adults (Ostrom et al, 2019)
Recent research focuses on the predictive value, and pathogenic mechanism of RING finger (RNF) proteins have been conducted in several cancer types

Summary

Introduction

Diffuse gliomas, including LGG and glioblastomas (GBM), are the most common malignant tumors among adults in the central nervous system (CNS) (Miller et al, 2019). Maximum safe surgical resection, radiotherapy, and chemotherapy remain the mainstay of therapeutic methods for gliomas (Zhang et al, 2019; Funakoshi et al, 2021). The prognosis of malignant and invasive gliomas is still far from satisfactory, even with recent improvements in diagnosis and. The RNF Family in Gliomas treatment methods (Tan et al, 2020; McKinnon et al, 2021). Nowadays, increasing evidence indicates that tumor immunotherapy focusing on blocking immune checkpoints has achieved remarkable benefits, providing a promising direction for glioma patients (Hodges et al, 2017; Aslan et al, 2020)

Methods

Results

Conclusion