# Integrated multi-omics analysis and experimental investigation of mitochondrial dynamics-related genes: molecular subtypes, immune landscape, and prognostic implications in lung adenocarcinoma

## TL;DR

This study explores how genes related to mitochondrial dynamics affect lung adenocarcinoma prognosis and immune response, identifying a new risk model and a potential drug target.

## Contribution

The study introduces a five-gene prognostic model and identifies MTCH2 as a potential therapeutic target in lung adenocarcinoma.

## Key findings

- Two distinct mitochondrial dynamics subtypes with different prognoses and immune profiles were identified.
- A five-gene risk score model was developed, showing better outcomes in low-risk patients.
- MTCH2 knockout reduced cancer cell growth and migration, suggesting its role as an adverse prognostic marker.

## Abstract

Lung adenocarcinoma (LUAD) is a common and aggressive subtype of lung cancer associated with poor clinical outcomes. The role of mitochondrial dynamics (MD)-related genes in tumor progression and immune regulation remains poorly understood.

Data from public databases were integrated, and subtypes were classified based on 23 MD-related genes. A five-gene prognostic model was constructed. Associations between the model and immune infiltration, tumor mutational burden (TMB), tumor stemness, and drug sensitivity were analyzed. The function of the key gene MTCH2 was validated through in vitro experiments.

Two distinct MD molecular subtypes were identified, exhibiting significant differences in prognosis and immune characteristics. A corresponding risk score model was established. Patients in the low-risk group showed better prognosis and enhanced immune activity, whereas the high-risk group displayed higher TMB and stemness scores. Drug sensitivity analysis revealed distinct responses to chemotherapeutic agents such as cisplatin and docetaxel between risk groups. Functional assays demonstrated that MTCH2 knockout significantly inhibited LUAD cell proliferation, migration, and invasion, and induced G0/G1 phase arrest, suggesting that MTCH2 may act as a potential adverse prognostic marker.

MD-related genes exhibit strong prognostic and immune subtyping value. The proposed risk model holds clinical potential, and MTCH2 may serve as a promising target for precision therapy in LUAD.