Low expression of lysosome-related genes KCNE1, NPC2, and SFTPD promote cancer cell proliferation and tumor associated M2 macrophage polarization in lung adenocarcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.This study identifies 18 lysosome-associated genes (LSAGs) linked to lung adenocarcinoma prognosis. Low expression of KCNE1, NPC2, and SFTPD promotes cancer growth and M2 macrophage polarization, offering insights for targeted lung cancer immunotherapy.
Area Of Science
- Oncology
- Molecular Biology
- Immunology
Background
- Lysosomes are crucial in malignancy by regulating tumor cell death.
- The role of lysosome-associated genes (LSAGs) in lung adenocarcinoma (LUAD) remains poorly understood.
Purpose Of The Study
- To identify and characterize LSAGs involved in LUAD prognosis.
- To develop a predictive model for LUAD patient outcomes based on LSAGs.
- To investigate the correlation between LSAGs, tumor microenvironment, and response to therapy.
Main Methods
- Identification and functional annotation of LSAGs using integrated single-cell and bulk RNA-sequencing data.
- Prognostic assessment of LSAGs via Cox and LASSO regression.
- Analysis of LSAG correlations with immune cell infiltration, chemotherapy, and immunotherapy.
- In vitro characterization of LSAG expression (KCNE1, NPC2, SFTPD) in LUAD cells and their impact on malignancy phenotypes.
Main Results
- Eighteen LSAGs associated with prognosis were identified; three (KCNE1, NPC2, SFTPD) formed a predictive model.
- High-risk LUAD patients exhibited poorer survival, with the model outperforming clinical indicators.
- LSAGs influenced immune cell infiltration (M0/M1 vs. M2 macrophages, dendritic cells) and predicted immunotherapy response.
- Low expression of KCNE1, NPC2, and SFTPD correlated with increased LUAD cell proliferation, invasion, and M2 macrophage polarization.
Conclusions
- A predictive signature based on KCNE1, NPC2, and SFTPD was developed and validated for LUAD patients.
- Downregulation of these LSAGs promotes LUAD progression and M2 macrophage polarization.
- Findings offer novel perspectives for developing personalized immunotherapy strategies in lung adenocarcinoma.
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