Construction of exosome non-coding RNA feature for non-invasive, early detection of gastric cancer patients by machine learning: a multi-cohort study

作者：Zerong Cai, Yongqiang Zheng, Yan Hu, Mengyao Ma, Yijin Wu, Jia Liu, Lu-Ping Yang, Jia‐Bo Zheng, Tian Tian, Peishan Hu, Zexian Liu, Lin Zhang, Rui-Hua Xu, Huai‐Qiang Ju · 发表于：Gut · 年份：2025 · DOI：10.1136/gutjnl-2024-333522 · 被引用次数：53 · 研究领域：Extracellular vesicles in disease、Cancer-related molecular mechanisms research、Ferroptosis and cancer prognosis

BACKGROUND AND OBJECTIVE: Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis. DESIGNS: Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves. RESULTS: RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score (cd-score), derived from the expression levels of four long ncRNAs (RP11.443C10.1, CTD-2339L15.3, LINC00567 and DiGeorge syndrome critical region gene (DGCR9)), was found to surpass commonly used biomarkers, such as carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and CA72-4, in distinguishing GC patients from healthy donors across training, testing and external validation cohorts, with AUC values of 0.959, 0.942 and 0.949, respectively. Additionally, the cd-score could effective...