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<p>This study aimed to identify essential genes driving lung adenocarcinoma (LUAD) progression by integrating CRISPR-Cas9 dependency data from the Cancer Dependency Map (DepMap) portal with transcriptomic profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Through a machine learning-based screening pipeline, we identified GINS complex subunit 1(GINS1) as a pivotal oncogenic driver in LUAD. Multi-omics analysis and in-house clinical validation confirmed that GINS1 is significantly upregulated at both mRNA and protein levels, serving as an independent prognostic marker. Functional assays demonstrated that GINS1 knockdown markedly inhibited LUAD cell proliferation and migration while inducing G1-phase arrest and apoptosis. Notably, GINS1 depletion sensitized tumor cells to ferroptosis, evidenced by increased reactive oxygen species (ROS) accumulation and a significant reduction in the Half Maximal Inhibitory Concentration (IC50) of the ferroptosis inducer Imidazole Ketone Erastin (IKE). Mechanistically, GINS1 promotes an immunosuppressive microenvironment by driving M2 macrophage polarization via the C-C Motif Chemokine Ligand 2(CCL2) axis and fostering T-cell exhaustion and immune exclusion. Clinically, high GINS1 expression predicted unfavorable responses to immune checkpoint blockade (ICB) therapy across multiple independent cohorts. In conclusion, our study identifies GINS1 as a central regulator of tumor cell survival and immune evasion, highlighting its potential as a prognostic biomarker and a promising therapeutic target for precision oncology in LUAD.</p>

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Multi-omics analysis identifies GINS1 as a prognostic biomarker in lung adenocarcinoma, linked to macrophage polarization and tumor cell survival

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Qi Xu,
  • Yantao Jiang,
  • Qingwu Du,
  • Jingya Wang,
  • Cong Wang,
  • Tingting Qin

摘要

This study aimed to identify essential genes driving lung adenocarcinoma (LUAD) progression by integrating CRISPR-Cas9 dependency data from the Cancer Dependency Map (DepMap) portal with transcriptomic profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Through a machine learning-based screening pipeline, we identified GINS complex subunit 1(GINS1) as a pivotal oncogenic driver in LUAD. Multi-omics analysis and in-house clinical validation confirmed that GINS1 is significantly upregulated at both mRNA and protein levels, serving as an independent prognostic marker. Functional assays demonstrated that GINS1 knockdown markedly inhibited LUAD cell proliferation and migration while inducing G1-phase arrest and apoptosis. Notably, GINS1 depletion sensitized tumor cells to ferroptosis, evidenced by increased reactive oxygen species (ROS) accumulation and a significant reduction in the Half Maximal Inhibitory Concentration (IC50) of the ferroptosis inducer Imidazole Ketone Erastin (IKE). Mechanistically, GINS1 promotes an immunosuppressive microenvironment by driving M2 macrophage polarization via the C-C Motif Chemokine Ligand 2(CCL2) axis and fostering T-cell exhaustion and immune exclusion. Clinically, high GINS1 expression predicted unfavorable responses to immune checkpoint blockade (ICB) therapy across multiple independent cohorts. In conclusion, our study identifies GINS1 as a central regulator of tumor cell survival and immune evasion, highlighting its potential as a prognostic biomarker and a promising therapeutic target for precision oncology in LUAD.