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<p>Mitochondrial autophagy (mitophagy) in macrophages is crucial yet poorly understood within the lung adenocarcinoma (LUAD) tumor microenvironment. This study aimed to identify key macrophage mitophagy-related genes and develop a robust prognostic model for LUAD patients. By integrating single-cell transcriptomics with machine learning algorithms, including LASSO, SVM, and random forest, we identified TUBB6 and CAT as core prognostic genes. A novel risk model based on these genes (RiskScore = 0.225 × TUBB6 − 0.19 × CAT) was constructed and validated, demonstrating that patients in the high-risk group had significantly shorter overall survival (<i>P</i> &lt; 0.001). The high-risk score also correlated with an altered immune microenvironment and increased sensitivity to chemotherapies like cisplatin and gemcitabine. Furthermore, in vitro experiments confirmed that macrophage-specific overexpression of TUBB6 significantly enhanced LUAD cell proliferation, migration, and invasion through secreted factors. Our findings establish a reliable, macrophage mitophagy-based prognostic model and highlight TUBB6 and CAT as novel biomarkers and potential therapeutic targets, offering new avenues for precision medicine in LUAD.</p>

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Macrophage mitophagy-related genes predict prognosis and therapeutic response in lung adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • TianRong Yang,
  • Qin Liu,
  • Wei Li,
  • Bin Pan,
  • JingFei Jiang,
  • HongMei Tan

摘要

Mitochondrial autophagy (mitophagy) in macrophages is crucial yet poorly understood within the lung adenocarcinoma (LUAD) tumor microenvironment. This study aimed to identify key macrophage mitophagy-related genes and develop a robust prognostic model for LUAD patients. By integrating single-cell transcriptomics with machine learning algorithms, including LASSO, SVM, and random forest, we identified TUBB6 and CAT as core prognostic genes. A novel risk model based on these genes (RiskScore = 0.225 × TUBB6 − 0.19 × CAT) was constructed and validated, demonstrating that patients in the high-risk group had significantly shorter overall survival (P < 0.001). The high-risk score also correlated with an altered immune microenvironment and increased sensitivity to chemotherapies like cisplatin and gemcitabine. Furthermore, in vitro experiments confirmed that macrophage-specific overexpression of TUBB6 significantly enhanced LUAD cell proliferation, migration, and invasion through secreted factors. Our findings establish a reliable, macrophage mitophagy-based prognostic model and highlight TUBB6 and CAT as novel biomarkers and potential therapeutic targets, offering new avenues for precision medicine in LUAD.