Non-invasive esophageal cancer screening in high-risk populations: a multi-omics integration model
Esophageal cancer (ESCA) is a leading cause of cancer-related mortality in China, with over 95% of patients diagnosed at advanced stages, resulting in low survival rates. Early detection is critical for improving outcomes, yet current screening methods are invasive or lack sensitivity. We developed a non-invasive early-detection model by integrating circulating cell-free DNA (cfDNA) methylation and fragmentomics features. Using a three-layer stacked ensemble machine learning framework, we analyzed multicenter blood samples from 309 participants, including ESCA patients and high-risk individuals. The integrated model called ESim-seq (Esophageal Cancer Screening with Integrated Model) achieved an AUC of 0.994 (95% CI: 0.979–1.000) in validation. At 99% specificity, sensitivity reached 87.3%, with simulated screening showing a 24.8% increase in stage I detection. Stratified analyses confirmed robustness across demographics, risk factors, and tumor stages. Clinical benefit modeling projected a 56.3% stage I detection rate under ideal conditions, significantly improving survival outcomes compared to standard care. This study developed a cfDNA-based analytical framework and demonstrated the advantage of multi-feature integration for early detection of ESCA.
Authors
- Xiangli Liu (ORCID: https://orcid.org/0000-0001-5951-9315)
- Mingrui Shao (ORCID: https://orcid.org/0000-0002-3543-3936)
- Xiaotong Xi (ORCID: https://orcid.org/0000-0002-9306-2942)
- Wanfu Men (ORCID: https://orcid.org/0000-0003-2968-1463)
- Xiaoqiang Wang (ORCID: https://orcid.org/0000-0001-9296-5421)
- Zhenghua Liu (ORCID: https://orcid.org/0009-0007-6418-8566)
- Peipei Zhang (ORCID: https://orcid.org/0000-0003-4405-0432)
- Xing Zhang (ORCID: https://orcid.org/0009-0004-8215-8000)
- Wenya Li (ORCID: https://orcid.org/0000-0002-5067-843X)
- Yue Wang (ORCID: https://orcid.org/0000-0003-0098-5359)
- Ying Liu (ORCID: https://orcid.org/0000-0001-8931-9656)
- Dongsheng Chen (ORCID: https://orcid.org/0000-0003-2400-0315)
- Ling Lv
- Yu Ding
- Shun Xu
- Huidong Yu
- Wanglong Deng
- Jingcai Wu
- Xiaohuan Hou
- Lei Ye
- Yong Li
- Youbin Cui
Institutions
- Chifeng University (CN)
- Jilin University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Wuhan Wudong Hospital (CN)
- National Cancer Center (US)
- Simcere Pharmaceutical (China) (CN)
- Chifeng Municipal Hospital (CN)
- First Hospital of Jilin University (CN)
- First Hospital of China Medical University (CN)
- Affiliated Hospital of Hebei University (CN)
- China Medical University (CN)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2026-07-23
- DOI
- https://doi.org/10.1038/s41698-026-01620-w
- Primary Topic
- Esophageal Cancer Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Medical University
- Department of Science and Technology of Liaoning Province
- Shengjing Hospital