Plasma
IFNL3
for Gastric Cancer Detection and Monitoring in East Asians: A Multiphase Study
Yunmeng Nie, Jihong Zhong, Siyi Ni, Yingchao Liu, Shuo Zhang, Guangji Zhang ABSTRACT
Background
Gastric cancer (GC) has a high incidence in East Asia, yet early detection remains limited.
Methods
In this multiphase study, 395 participants (96 GC, 72 precancerous lesions, 227 healthy donors) were enrolled. Plasma IFNL3 levels were measured using ELISA. Mendelian randomization was used to assess the causality between IFNL3 and GC. Receiver operating characteristic curves were used to calculate diagnostic efficiency in comparison between IFNL3 and traditional biomarkers (alpha fetoprotein [AFP], carcinoembryonic antigen [CEA], and cancer antigen 19‐9 [CA19‐9]).
Results
Bidirectional Mendelian randomization analysis suggested a potential association between plasma IFNL3 and GC in East Asians. In Test phase, plasma IFNL3 demonstrated superior diagnostic performance in differentiating GC from HDs (AUC = 0.901, 95% CI: 0.866–0.935) compared to AFP, CEA, and CA19‐9. IFNL3 levels correlated with disease progression, increasing progressively across clinical stages. IFNL3 mRNA was also higher in cancerous tissues compared to normal and para‐cancerous tissues. In Validation phase, IFNL3 exhibited high diagnostic specificity. In Extension phase, plasma IFNL3 showed distinct diagnostic potential for differentiating chronic non‐atrophic gastritis (CNAG), atrophic intestinal metaplasia (AIM), low‐grade intraepithelial neoplasia (LGIN), and high‐grade intraepithelial neoplasia (HGIN).
Conclusions
Plasma IFNL3 levels were increased in gastric cancer and correlated with disease progression. However, its value as a diagnostic biomarker requires validation in larger, stage‐adjusted studies.