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Non-small cell lung cancer subtype classification based on cross-scale multi-instance learning
Peihe Jiang1, Weilong Chen1, Guibin Zheng2
1School of Physics and Electronic Information, Yantai University, Yantai, 264005, China.
Scientific Reports
|December 5, 2025
Summary
A new AI model accurately classifies lung cancer subtypes (LUAD and LUSC) using pathological images. This advanced tool shows high accuracy and strong generalization, aiding in precise non-small cell lung cancer diagnosis.
Area of Science:
- Computational pathology
- Artificial intelligence in oncology
- Medical image analysis
Background:
- Non-small cell lung cancer (NSCLC) subtypes, including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), pose diagnostic challenges impacting treatment.
- Accurate subtype classification is crucial for effective NSCLC treatment planning.
Purpose of the Study:
- To develop and validate a novel multi-instance learning (MIL) model for enhanced pathological image classification of NSCLC subtypes.
- To improve the accuracy and reliability of differentiating LUAD from LUSC using computational pathology.
Main Methods:
- A novel MIL model incorporating an additive attention mechanism and a category classifier was developed.
- A cross-scale focal region detection strategy was integrated to enhance feature sensitivity.
- The model was trained on the Cancer Genome Atlas (TCGA) dataset and validated on CPTAC TCIA and external hospital datasets.
Main Results:
- The model achieved 97.0% accuracy (ACC) and 0.978 area under the ROC curve (AUC) on the TCGA dataset, outperforming existing methods.
- Validation on external datasets showed robust performance with ACCs of 91.2% and 93.0%, and AUCs of 0.967 and 0.968.
- Ablation studies confirmed the significant contribution of each model component to performance.
Conclusions:
- The proposed MIL model demonstrates superior performance in classifying LUAD and LUSC subtypes.
- The model exhibits strong generalization capabilities across diverse datasets, indicating its potential for clinical application.
- This AI-driven approach offers a reliable tool for accurate NSCLC subtype diagnosis and improved patient management.

