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This study proposes an Efficient and Explainable Ensemble-learning framework (EEE-framework) designed for early detection of non-small cell lung cancer (NSCLC) biomarkers using gene expression data, specifically addressing challenges of interpretability in detection outcomes. The EEEframework comprises two core modules. The first module constructs an ensemble-learning model balancing detection accuracy and interpretability. Considering the typical trade-off between accuracy and interpretability, we explore various combinations of 10 individual learners, ultimately selecting five (Decision Tree, Random Forest, XGBoost, AdaBoost, and Gaussian Naive Bayes) with high interpretability as base learners. Subsequently, we classify NSCLC by integrating votingensemble with high interpretability. The second module develops a multi-perspective approach to identify important NSCLC biomarkers using six explainable artificial intelligence (XAI) methods, ranging from Local to Global Interpretability and from Intrinsic to Post-hoc Interpretability. The EEE-framework's generalization ability and interpretability are validated using the TCGA RNA_seq public dataset and a self-constructed methylation dataset. Validation results demonstrate the exceptional classification performance of the ensemble-learning model integrated in the framework, achieving F1 values of 0.9983(Area Under the Curve/AUC:0.9993) and 0.8462(AUC:0.9249) on the two datasets, respectively. Global and Local Interpretable Visualization results significantly enhance the diagnosis and understanding of NSCLC biomarkers, providing insights to their importance rankings, interrelationships, and causality with predicted outcomes.
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http://dx.doi.org/10.1109/TCBBIO.2025.3605045 | DOI Listing |
Front Immunol
September 2025
Department of Thoracic Surgery, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China.
Background: Lung cancer remains the leading cause of cancer-related mortality globally, primarily due to late-stage diagnosis, molecular heterogeneity, and therapy resistance. Key biomarkers such as EGFR, ALK, KRAS, and PD-1 have revolutionized precision oncology; however, comprehensive structural and clinical validation of these targets is crucial to enhance therapeutic efficacy.
Methods: Protein sequences for EGFR, ALK, KRAS, and PD-1 were retrieved from UniProt and modeled using SWISS-MODEL to generate high-confidence 3D structures.
JTO Clin Res Rep
October 2025
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden.
Introduction: Immune checkpoint blockade (ICB) is a standard first-line treatment for stage IV NSCLC without actionable oncogenic alterations. mutations, prevalent in 30% to 40% lung adenocarcinomas (LUAD) in Western populations, currently lack targeted first-line therapies. This study aimed to assess the predictive value of mutations for clinical outcomes after distinct ICB regimens, validating our previous findings in a larger cohort with extended follow-up.
View Article and Find Full Text PDFZhonghua Jie He He Hu Xi Za Zhi
September 2025
Department of nursing, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are important treatments for EGFR mutant non-small cell lung cancer (NSCLC). However, the first and second generation EGFR-TKI face clinical limitations due to acquired resistance, such as the T790M mutation. Irreversible EGFR-TKI can significantly prolong the survival of patients by enhancing the inhibition of drug-resistant mutations through the covalent binding mechanism.
View Article and Find Full Text PDFLung Cancer
September 2025
Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan; Division of Next-Generation Drug Development Research, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Ni
Background: The risk factors associated with treatment resistance to consolidation durvalumab following chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) have not been well established.
Methods: Extracellular vesicles (EVs) were isolated from the pretreatment serum of 73 patients treated with consolidation durvalumab. Isolation was performed using CD9/CD63 antibodies, and EV proteins were identified using liquid chromatography-tandem mass spectrometry (LC-MS).
Eur Radiol
September 2025
Quantitative Imaging Biomarkers in Medicine, Quibim, Valencia, Spain.
Objectives: In non-small cell lung cancer (NSCLC), non-invasive alternatives to biopsy-dependent driver mutation analysis are needed. We reviewed the effectiveness of radiomics alone or with clinical data and assessed the performance of artificial intelligence (AI) models in predicting oncogene mutation status.
Materials And Methods: A PRISMA-compliant literature review for studies predicting oncogene mutation status in NSCLC patients using radiomics was conducted by a multidisciplinary team.