Prediction of prognosis and immune response in lung adenocarcinoma based on mitophagy and lactate-related gene signatures

Lung adenocarcinoma (LUAD) causes leading death worldwide. Mitophagy and lactate metabolism accumulation are distinctive features of LUAD. We aimed to identify lactate-related genes (LRGs) signatures based on mitophagy for predicting prognosis and immune response in LUAD.

The gene expression and clinical data were downloaded from TCGA and GEO database. First, the subtype analysis was analyzed based on 29 mitophagy genes. Survival, immune, and function differences between the different subtypes were analyzed. Then, based on mitophagy genes and 14 LRGs, the best LRGs were screened to construct a risk score model and combined with clinical factors to establish a nomogram for predicting patient survival. Finally, the expression level and molecular function of the key candidate gene OGDH were verified by in vitro experiments.

All the LUAD samples were divided into 2 subtypes: sub1 and sub2. The sub2 possessed worse survival. Immune score, immune checkpoint genes, and human leucocyte antigen genes in sub1 were higher than in sub2. Six optimal mitophagy-related LRGs were used to construct a risk score model. A high-risk score indicates poorer survival, higher tumor mutation burden, and higher drug sensitivity. The nomogram was robust in predicting LUAD survival. The experiments in vitro showed that knockdown of OGDH inhibited the proliferation, migration and invasion in LUAD cells.

A nomogram based on the construction of the mitophagy-related lactate genes predicts prognosis and immune response in LUAD. These results could help with risk stratification and targeted therapy for LUAD.