Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets

Journal of Translational Medicine

Runmei Li¹  Yiwei Huang²  Qun Wang²  Tao Lu²  Jiacheng Yin²  Cheng Zhan²  Yunyi Bian²  Jiaqi Liang²  Mengnan Zhao²  Hong Fan²  Guoshu Bi² 

[1] Department of Biostatistics, Public Health, Fudan University, 200000, Shanghai, China;Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, 200032, Shanghai, China;

关键词: Metabolism;    Glycolysis;    Pan-cancer;    Oxidative phosphorylation;    Warburg effect;   

DOI  :  10.1186/s12967-021-02889-0

来源: Springer

【 摘 要 】

BackgroundGenerally, cancer cells undergo metabolic reprogramming to adapt to energetic and biosynthetic requirements that support their uncontrolled proliferation. However, the mutual relationship between two critical metabolic pathways, glycolysis and oxidative phosphorylation (OXPHOS), remains poorly defined.MethodsWe developed a “double-score” system to quantify glycolysis and OXPHOS in 9668 patients across 33 tumor types from The Cancer Genome Atlas and classified them into four metabolic subtypes. Multi-omics bioinformatical analyses was conducted to detect metabolism-related molecular features.ResultsCompared with patients with low glycolysis and high OXPHOS (LGHO), those with high glycolysis and low OXPHOS (HGLO) were consistently associated with worse prognosis. We identified common dysregulated molecular features between different metabolic subgroups across multiple cancers, including gene, miRNA, transcription factor, methylation, and somatic alteration, as well as investigated their mutual interfering relationships.ConclusionOverall, this work provides a comprehensive atlas of metabolic heterogeneity on a pan-cancer scale and identified several potential drivers of metabolic rewiring, suggesting corresponding prognostic and therapeutic utility.

【 授权许可】

CC BY