A Novel Risk Score Model of Lactate Metabolism for Predicting over Survival and Immune Signature in Lung Adenocarcinoma

作者：Zhou Jiang, Yongzhong Luo, Lemeng Zhang, Haitao Li, Changqie Pan, Hua Yang, Tianli Cheng, Jianhua Chen · 发表于：Cancers · 年份：2022 · DOI：10.3390/cancers14153727 · 被引用次数：22 · 研究领域：Cancer, Hypoxia, and Metabolism、Ferroptosis and cancer prognosis、Lung Cancer Treatments and Mutations

BACKGROUND: The role of lactate acid in tumor progression was well proved. Recently, it was found that lactate acid accumulation induced an immunosuppressive microenvironment. However, these results were based on a single gene and it was unclear that lactate acid genes were associated with immunotherapy and able to predict overall survival. METHODS: Genes and survival data were acquired from TCGA, GEO and GENECARDS. PCA and TSNE were used to distinguish sample types according to lactate metabolism-associated gene expression. A Wilcox-test examined the expression differences between normal and tumor samples. The distribution in chromatin and mutant levels were displayed by Circo and MAfTools. The lactate metabolism-associated gene were divided into categories by consistent clustering and visualized by Cytoscape. Immune cell infiltration was evaluated by CIBERSORT and LM22 matrix. Enrichment analysis was performed by GSVA. We used the ConsensusClusterPlus package for consistent cluster analysis. A prognostic model was constructed by Univariate Cox regression and Lasso regression analysis. Clinical specimens were detected their expression of genes in model by IHC. RESULTS: Most lactate metabolism-associated gene were significantly differently expressed between normal and tumor samples. There was a strong correlation between the expression of lactate metabolism-associated gene and the abundance of immune cells. We divided them into two clusters (lactate.cluster A,B) with signific...