Lactate gene signature based on mitophagy predict the prognosis and immune response in lung adenocarcinoma

Abstract

Abstract Background Lung adenocarcinoma (LUAD) causes leading death worldwide. Mitophagy and release of lactate is critical feature in tumor environment. We aimed to identified a mitophagy relate lactate related gene (LRG) signature for predicting prognosis and immune response in LUAD. Methods The gene expression and clinical data were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Firstly, according to the 29 mitophagy genes from Pathway Unification database, the subtype analysis analyzed using ConsensusClusterP lus. Survival, clinical, immune, and function differences between the two subtypes were analyzed. Then, based on the mitophagy genes and 14 LRGs from MSigDBv7.5.1 database, weighed gene co-expression network analysis (WGCNA) and univariate cox analysis were used to screen the optimal LRGs genes. A risk score model was established based on the optimal LRGs genes. Survival, mutation, drug sensitivity, and immune feature between high- and low-risk groups were also analyzed. Furthermore, the distribution of risk score indifferent subtypes were also explored. Finally, based on the risk score and clinical factors, a nomogram for predicting the patient survival were established. Results All the LUAD samples were divided into 2 subtypes: sub 1 and sub 2. Sub 2 possessed worse survival (P < 0.05). Immune score, immune checkpoint genes, human leucocyte antigen genes in sub2 were higher than in sub 1, suggesting an active immune microenvironment in sub 2. Six optimal mitophagy-related LRGs (LDHA, PLEC, DARS2, ACAT1, C1QBP, and OGDH) were used to construct a risk score model and the model was effective in predicting the survival of LUAD patients. High-risk score indicates a poorer survival, higher tumor mutation burden, and higher drug sensitivity. Furthermore, sub 2 contained more high-risk samples, further demonstrating the predicting ability of the subtypes and risk score groups. Finally, nomogram was also robust in predicting LUAD survival with AUC more than 0.7. Conclusion These results are useful for prognosis of survival and immune status, as well as provide indication for patient drug option in LUAD.