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

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.754873

DOI=10.3389/fcell.2021.754873

ISSN=2296-634X

ABSTRACT=Increasing evidence has demonstrated that really interesting new gene (RING) finger (RNF) proteins can regulate the transport and activity of molecules, which play a vital role in many aspects of cellular and physiological processes. However, the function of RNF proteins in low-grade glioma (LGG) remains unknown. First, a total of 138 RNF family members were involved in this study. The TCGA database was used as the training cohort; the other two databases were selected as external validation cohorts. Secondly, we divided patients into two subgroups using consensus clustering analysis and compared the outcome using the Kaplan–Meier curve. Thirdly, ESTIMATE, CIBERSORT, xCell, and IMMUNOGRAM algorithms were performed to depict the immune landscapes. Meanwhile, the enrichment pathways were confirmed by GO and KEGG databases. Finally, main contributors were found through machine learning, and sensitive drugs between clusters were predicted. Patients were grouped into cluster 1 and cluster 2, both in the training and validation cohorts. The prognosis of patients in cluster 1 is significantly better than that in cluster 2, and they have good clinicopathological characteristics, including IDH mutation and IDH mut-codel subtype. On the other hand, cluster 2 showed different immune infiltrated and immunosuppressive features in the tumor microenvironment (TME) from cluster 1 and were enriched with signaling 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. In addition, various targeted and small molecule drugs are sensitive to patients in cluster 2. Importantly, we discovered TRIM8, DTX2, and TRAF5 as the most vital contributors from the RNF family, which were related to immune infiltration in LGG TME. 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.