Machine learning-based identification of glycosyltransferase-related mRNAs for improving outcomes and the anti-tumor therapeutic response of gliomas

School of Medicine ,Tongji University ,Shanghai ,China
Zhang, Chunyu;
Department of Anesthesiology ,Huzhou Central Hospital ,The Affiliated Huzhou Hospital ,Zhejiang University School of Medicine ,Huzhou ,Zhejiang ,China
Zhou, Wei

Background: Glycosyltransferase participates in glycosylation modification, and glycosyltransferase alterations are involved in carcinogenesis, progression, and immune evasion, leading to poor outcomes. However, in-depth studies on the influence of glycosyltransferase on clinical outcomes and treatments are lacking. Methods: The analysis of differentially expressed genes was performed using the Gene Expression Profiling Interactive Analysis 2 database. A total of 10 machine learning algorithms were introduced, namely, random survival forest, elastic network, least absolute shrinkage and selection operator, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox, supervised principal components, generalized boosted regression modeling, and survival support vector machine. Gene Set Enrichment Analysis was performed to explore signaling pathways regulated by the signature. Cell-type identification by estimating relative subsets of RNA transcripts was used for estimating the fractions of immune cell types. Results: Here, we analyzed the genomic and expressive alterations in glycosyltransferase-related genes in gliomas. A combination of 80 machine learning algorithms was introduced to establish the glycosyltransferase-related mRNA signature (GRMS) based on 2,030 glioma samples from The Cancer Genome Atlas Program, Chinese Glioma Genome Atlas, Rembrandt, Gravendeel, and Kamoun cohorts. The GRMS was identified as an independent hazardous factor for overall survival and exhibited stable and robust performance. Notably, gliomas in the high-GRMS subgroup exhibited abundant tumor-infiltrating lymphocytes and tumor mutation burden values, increased expressive levels of hepatitis A virus cellular receptor 2 and CD274, and improved progression-free survival when subjected to anti-tumor immunotherapy. Conclusion: The GRMS may act as a powerful and promising biomarker for improving the clinical prognosis of glioma patients.


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