To construct a mitochondrial-related risk assessment model to explore the impact of mitochondria on the survival of patients with non-small cell lung cancer (NSCLC), predict immune status, and evaluate its potential value.

Mitochondrial and NSCLC-related data were downloaded from the MitoCarta3.0 database and The Cancer Genome Atlas (TCGA) database, respectively. Differentially expressed mitochondrial-related genes were screened, and a risk scoring model was constructed using Cox regression analysis. Based on the median risk score, NSCLC patients in the TCGA database were divided into high-risk and low-risk groups. The validity of the prognostic model was verified using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, clinical case feature analysis, and immune status assessment.

A total of 320 mitochondrial-related genes were obtained from NSCLC samples. Four key model genes (TIMM10, CYP24A1, BCL2L10, ACSM5) were selected through COX analysis, leading to the construction of a nomogram prediction model for NSCLC. Immune cell infiltration assessment revealed a negative correlation between risk scores and the enrichment of T cells, B cells, and macrophages; conversely, the enrichment of resting mast cells, cancer-associated fibroblasts, and myeloid progenitor cells was positively correlated with risk scores. Patients in the high-risk group had shorter overall survival and exhibited higher levels of immune suppressive cell infiltration. Validation of the IMvigor210 immunotherapy model showed significant differences in survival probabilities between high-risk and low-risk groups in bladder cancer.

This study established a mitochondrial gene risk scoring model for predicting the prognosis of NSCLC. TIMM10,CYP24A1, BCL2L10, and ACSM5 are promising potential targets for further research on NSCLC.