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2000
Volume 21, Issue 9
  • ISSN: 1573-4110
  • E-ISSN: 1875-6727

Abstract

Introduction

Lung adenocarcinoma (LUAD) exhibits high incidence and mortality rates globally. Mitophagy exerts a critical role in cancer development, including LUAD. The present work set out to classify the molecular subtypes of LUAD and to develop a mitophagy-related gene (MRG) signature to assess the prognostic outcomes of LUAD patients.

Methods

Two datasets were acquired from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. MRGs were extracted from the MSigDB. The somatic gene mutation landscape was developed using the “maftools” package. Molecular subtypes were classified by employing the “ConsensusClusterPlus” package. Functional enrichment analysis was performed using the “clusterProfiler” package. Mitophagy-related module genes were identified using the “WGCNA” package and used to develop a prognostic MRG signature employing LASSO Cox regression analysis. Then, a RiskScore model was formulated and validated. Immune cell infiltration in different groups was compared. The expressions of the prognostic MRGs in LUAD cells were detected by tests. CCK-8, wound healing, and transwell assays were carried out to measure the cell viability, and migratory and invasive capabilities of LUAD cells.

Results

Somatic gene mutation was detected in 77 (13.58%) out of 567 LUAD patients and 10 (50%) out of 20 prognosis-related MRGs. Based on 20 prognosis-related MRGs, three molecular LUAD subtypes with distinct prognostic outcomes, clinical features, immune cell infiltration, and biological pathways were classified. Next, a 9-MRG signature composed of 3 “protective” genes (, , ) and 6 “risk” genes (, , , , , ) was established. Then, a RiskScore model with excellent prognostic predictive power for LUAD was constructed. The high-risk group showed worse outcomes and decreased immune cell infiltration in comparison to the low-risk group. Further, the relative mRNA expressions of , , and were significantly downregulated, while those of , , , , , and were notably upregulated in LUAD cells. In addition, silencing and significantly affected the invasive and migratory capacities of LUAD cells.

Conclusion

We delineated three molecular subtypes and developed a 9-MRG signature in LUAD, providing a valuable framework for the prognosis evaluation of LUAD patients.

© 2025 Bentham Science Publishers
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Classification of Molecular Subtypes and Establishment of a Mitophagy-related Gene Signature to Predict the Prognostic Outcomes for Lung Adenocarcinoma Patients
Current Analytical Chemistry 21, 1261 (2025); https://doi.org/10.2174/0115734110370974250117074604
/content/journals/cac/10.2174/0115734110370974250117074604
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  • Article Type:     Research Article
Keyword(s): gene signature; immune cells infiltration; lung adenocarcinoma; Mitophagy; molecular subtypes; prognosis; RiskScore model

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