journal article·2025-06Open access

Single‐Cell Sequencing‐Guided Annotation of Rare Tumor Cells for Deep Learning‐Based Cytopathologic Diagnosis of Early Lung Cancer

Yichun Zhao, Ruoran Qiu, Zhuo Wang, Yunyun Li, Xu Yang, Yanlin Li, Xiaohan Shen, Yun Liu, Ziqiang Chen, Qihan You, Qihui Shi

Advanced Science· Volume 12· Issue 22

Abstract

Abstract Deep learning (DL) models for medical image analysis are majorly bottlenecked by the lack of well‐annotated datasets. Bronchoalveolar lavage (BAL) is a minimally invasive procedure to diagnose lung cancer, but BAL cytology suffers from low sensitivity. The success of DL in BAL cytology is rare due to the rarity of exfoliated tumor cells (ETCs) and their subtle morphological differences from normal cells. Single‐cell DNA sequencing (scDNA‐Seq) is utilized as an objective ground truth of ETC annotation for generating an unbiased, accurately annotated dataset comprising 580 ETCs and 1106 benign cells from BAL cytology slides. A DL model is developed, to distinguish ETC from benign cells in BAL fluid, achieving an Area Under the Curve of 0.997 and 0.956 for detecting large‐ and small‐sized ETCs, respectively. The model is applied in a discovery cohort (n = 156) to establish BAL‐based cytopathologic diagnostic model for lung cancer. The model is evaluated in a validation cohort (n = 158), and yielded 47.6% sensitivity and 97.7% specificity in lung cancer diagnosis, outperforming cytology with improved sensitivity (47.6% vs 19.0%). In an external validation cohort (n = 141), the model achieved 60.0% sensitivity and 92.5% specificity in lung cancer diagnosis.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cancer Genomics and Diagnostics · Lung Cancer Diagnosis and Treatment · AI in cancer detection

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Whole‐Period Monitoring and Precise Intervention of Digestive Cancer (SMHC) Minhang Hospital and Institutes of Biomedical Sciences Fudan University Shanghai 200032 China

Department of Pathology The First Affiliated Hospital (Qingchun campus) Zhejiang University School of Medicine Hangzhou 310003 China

Department of Pathology The First Affiliated Hospital (Yuhang campus) Zhejiang University School of Medicine Hangzhou 311121 China

Department of Pathology Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan 250117 China

MOE Key Laboratory of Metabolism and Molecular Medicine Department of Biochemistry and Molecular Biology School of Basic Medical Sciences and Shanghai Xuhui Central Hospital Fudan University Shanghai 200032 China

Shanghai Engineering Research Center of Biomedical Analysis Reagents Fudan Zhang Jiang Institute Shanghai 201203 China

Funding

National Natural Science Foundation of China · Program of Shanghai Academic Research Leader · Key Technologies Research and Development Program

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