ESCCPred: a machine learning model for diagnostic prediction of early esophageal squamous cell carcinoma using autoantibody profiles

• Published in: British journal of cancer Vol. 131; no. 5; pp. 883 - 894
• Main Authors: Li, Tiandong, Sun, Guiying, Ye, Hua, Song, Caijuan, Shen, Yajing, Cheng, Yifan, Zou, Yuanlin, Fang, Zhaoyang, Shi, Jianxiang, Wang, Keyan, Dai, Liping, Wang, Peng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.09.2024; Nature Publishing Group
• Subjects: 631/250/580; 631/67/1857; 692/53/2421; Aged; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Early Detection of Cancer - methods; Enzyme-linked immunosorbent assay; Epidemiology; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - blood; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - immunology; Esophageal Squamous Cell Carcinoma - blood; Esophageal Squamous Cell Carcinoma - diagnosis; Esophageal Squamous Cell Carcinoma - immunology; Female; HSF1 protein; Humans; Learning algorithms; Machine Learning; Male; Medical diagnosis; Middle Aged; Molecular Medicine; Oncology; Prediction models; Proteomes; Public health; ROC Curve; SNAP-25 protein; Squamous cell carcinoma; Support Vector Machine; Support vector machines
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-024-02781-w

Background Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with no clinically ideal biomarkers for early diagnosis. The objective of this study was to develop and validate a user-friendly diagnostic tool for early ESCC detection. Methods The study encompassed three phases: discovery, verification, and validation, comprising a total of 1309 individuals. Serum autoantibodies were profiled using the HuProt TM human proteome microarray, and autoantibody levels were measured using the enzyme-linked immunosorbent assay (ELISA). Twelve machine learning algorithms were employed to construct diagnostic models, and evaluated using the area under the receiver operating characteristic curve (AUC). The model application was facilitated through R Shiny, providing a graphical interface. Results Thirteen autoantibodies targeting TAAs (CAST, FAM131A, GABPA, HDAC1, HDGFL1, HSF1, ISM2, PTMS, RNF219, SMARCE1, SNAP25, SRPK2, and ZPR1) were identified in the discovery phase. Subsequent verification and validation phases identified five TAAbs (anti-CAST, anti-HDAC1, anti-HSF1, anti-PTMS, and anti-ZPR1) that exhibited significant differences between ESCC and control subjects ( P  < 0.05). The support vector machine (SVM) model demonstrated robust performance, with AUCs of 0.86 (95% CI: 0.82–0.89) in the training set and 0.83 (95% CI: 0.78–0.88) in the test set. For early-stage ESCC, the SVM model achieved AUCs of 0.83 (95% CI: 0.79–0.88) in the training set and 0.83 (95% CI: 0.77–0.90) in the test set. Notably, promising results were observed for high-grade intraepithelial neoplasia, with an AUC of 0.87 (95% CI: 0.77–0.98). The web-based implementation of the early ESCC diagnostic tool is publicly accessible at https://litdong.shinyapps.io/ESCCPred/ . Conclusion This study provides a promising and easy-to-use diagnostic prediction model for early ESCC detection. It holds promise for improving early detection strategies and has potential implications for public health.