AUTHOR=Chen Zigui , Liu Chao , Zhang Chunyuan , Xia Ying , Peng Jun , Miao Changfeng , Luo Qisheng TITLE=Machine learning-based discovery of UPP1 as a key oncogene in tumorigenesis and immune escape in gliomas JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1475206 DOI=10.3389/fimmu.2024.1475206 ISSN=1664-3224 ABSTRACT=Introduction

Gliomas are the most common and aggressive type of primary brain tumor, with a poor prognosis despite current treatment approaches. Understanding the molecular mechanisms underlying glioma development and progression is critical for improving therapies and patient outcomes.

Methods

The current study comprehensively analyzed large-scale single-cell RNA sequencing and bulk RNA sequencing of glioma samples. By utilizing a series of advanced computational methods, this integrative approach identified the gene UPP1 (Uridine Phosphorylase 1) as a novel driver of glioma tumorigenesis and immune evasion.

Results

High levels of UPP1 were linked to poor survival rates in patients. Functional experiments demonstrated that UPP1 promotes tumor cell proliferation and invasion and suppresses anti-tumor immune responses. Moreover, UPP1 was found to be an effective predictor of mutation patterns, drug response, immunotherapy effectiveness, and immune characteristics.

Conclusions

These findings highlight the power of combining diverse machine learning methods to identify valuable clinical markers involved in glioma pathogenesis. Identifying UPP1 as a tumor growth and immune escape driver may be a promising therapeutic target for this devastating disease.