Longitudinal Tracking of Chromosomal Instability Informs Timely Intervention in the Gastric Precancerous Cascade
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Background
A major unmet need in gastric cancer prevention is the lack of biomarkers to predict precancerous lesion progression, and the potential of chromosomal instability (CIN) for this role, particularly regarding early cancer and recurrence, remains unclear.
Objective
To assess the predictive role of CIN in lesion progression and postoperative recurrence following endoscopic submucosal dissection (ESD).
Design
We enrolled 106 patients from Taizhou Hospital Affiliated to Wenzhou Medical University (2011–2025) and collected 1,045 temporally continuous pathological samples.
Copy number variations were profiled using low-coverage whole-genome sequencing (LC-WGS), and CIN scores were calculated. Associations between CIN and clinical outcomes were analyzed using survival analysis and ROC curves.
Results
CIN was detectable up to two years before gastric cancer diagnosis, with positivity rates increasing alongside lesion severity: 25.5% in intestinal metaplasia, 39.7% in low-grade dysplasia, and 83.0% in gastric cancer. CIN positivity independently predicted lesion progression (hazard ratio [HR] = 2.55, 95% CI: 1.19–5.47, p = 0.016), with the greatest risk for progression to carcinoma (HR = 16.61, p < 0.001). The predictive AUC was 0.81, improving to 0.88 when combined with age. Among 84 patients who underwent ESD, CIN positivity significantly increased recurrence risk (HR = 19.57, 95% CI: 2.59 – 147.61, p = 0.004; AUC = 0.80). Chromosomal arms 7p/q, 8p/q, and 20p/q showed high CIN frequencies, with MYC being the most frequently mutated oncogene.
Conclusion
CIN represents a reliable biomarker for early prediction of lesion progression and postoperative recurrence, enabling proactive surveillance and precision management of gastric cancer.
Single Sentence Summary
Chromosomal instability (CIN) acts as a reliable biomarker for predicting the progression of gastric precancerous lesions and postoperative recurrence.
