Role of glycosphingolipid biosynthesis coregulators in malignant progression of thymoma

胸腺瘤 小桶 生物 前纵隔 转录组 代谢组学 代谢途径 计算生物学 基因 癌症研究 生物信息学 遗传学 免疫学 纵隔 基因表达 解剖
作者
Xin Zhang,Bo Zeng,Haijing Zhu,Rui Ma,Peng Yuan,Zhenguang Chen,Chunhua Su,Zhihao Liu,Xiaojing Yao,Anthony J. Lawrence,Zhenguo Liu,Jianyong Zou
出处
期刊:International Journal of Biological Sciences [Ivyspring International Publisher]
卷期号:19 (14): 4442-4456 被引量:2
标识
DOI:10.7150/ijbs.83468
摘要

As the most common malignancy from mediastinum, the metabolic reprogramming of thymoma is important in its development. Nevertheless, the connection between the metabolic map and thymoma development is yet to be discovered. Thymoma was categorized into three subcategories by unsupervised clustering of molecular markers for metabolic pathway presentation in the TCGA dataset. Different genes and functions enriched were demonstrated through the utilization of metabolic Gene Ontology (GO) analysis. To identify the main contributors in the development of thymic malignancy, we utilized Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The prognosis of thymoma was evaluated by screening the essential pathways and genes using GSVA scores and machine learning classifiers. Furthermore, we integrated the transcriptomics findings with spectrum metabolomics investigation, detected through LC-MS/MS, in order to establish the essential controller network of metabolic reprogramming during thymoma progression. The thymoma prognosis is related to glycosphingolipid biosynthesis-lacto and neolacto series pathway, of what high B3GNT5 indicate poor survival. The investigation revealed that glycosphingolipid charts have a significant impact on metabolic dysfunction and could potentially serve as crucial targets in the clinical advancement of metabolic therapy.
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