Identifying metabolic reprogramming phenotypes with glycolysis-lipid metabolism discoordination and intercellular communication for lung adenocarcinoma metastasis

• DOI: 10.1038/s42003-022-03135-z
• Publication Date: 2022-03-17T11:04:45Z
• Authors: Xin Li; Lefan Tang; Jiaxing Deng; Xiuying Qi; Juxuan Zhang; Haitao Qi; Mengyue Li; Yixin Liu; Wenyuan Zhao; Yunyan Gu; Lishuang Qi; Xia Li
• Keywords: Reprogramming

Abstract Tumor metastasis imposes metabolic requirements for escaping from primary tissues, producing vulnerability in treatment. This study aimed to explore the reprogramming relevant lung adenocarcinoma (LUAD) and decode underlying intercellular alterations. Using gene expression profiles of 394 LUAD samples derived The Cancer Genome Atlas (TCGA), we identified 11 metastasis-related genes involved glycolysis lipid metabolism, defined three phenotypes (MP-I, -II, -III) using unsupervised clustering. MP-III with highest glycolytic lowest levels exhibited metastatic potency poorest survival TCGA six independent cohorts totaling 1,235 samples. Genomic analyses showed that mutations TP53 KEAP1 , deletions SETD2 PBRM1 might drive MP-III. Single-cell RNA-sequencing data validated a evolutionary trajectory normal MP-II MP-III, through MP-I. further communications revealed interacted uniquely endothelial cells fibroblasts ANGPTL pathway, had stronger interactions VEGF pathway. Herein, glycolysis-lipid dysregulation patterns suggested metastasis. Further insights into oncogenic drivers microenvironmental would facilitate treatment future.