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Peer-reviewedCC BY-NC-ND 4.0Cancer Medicine

Plasma IFNL3 for Gastric Cancer Detection and Monitoring in East Asians: A Multiphase Study

  • Yunmeng Nie1,2
  • Jihong Zhong1,2
  • Siyi Ni1
  • Yingchao Liu1,2
  • Shuo Zhang1,2
  • Guangji Zhang3,4
4 affiliations
  1. 1Department of Gastroenterology The Second Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou People's Republic of China
  2. 2Key Laboratory of Traditional Chinese Medicine for the Treatment of Intestine‐Liver of Zhejiang Province Hangzhou People's Republic of China
  3. 3School of Basic Medical Sciences Zhejiang Chinese Medical University Hangzhou People's Republic of China
  4. 4Zhejiang Key Laboratory of Blood‐Stasis‐Toxin Syndrome Hangzhou People's Republic of China
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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.

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Cite

BibTeXRIS
BibTeX
@article{nie2026plasma,
  title = {{Plasma IFNL3 for Gastric Cancer Detection and Monitoring in East Asians: A Multiphase Study}},
  author = {Yunmeng Nie and Jihong Zhong and Siyi Ni and Yingchao Liu and Shuo Zhang and Guangji Zhang},
  journal = {Cancer Medicine},
  year = {2026},
  month = nov,
  doi = {10.1002/cam4.72381},
  url = {https://doi.org/10.1002/cam4.72381},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Plasma IFNL3 for Gastric Cancer Detection and Monitoring in East Asians: A Multiphase Study
AU  - Yunmeng Nie
AU  - Jihong Zhong
AU  - Siyi Ni
AU  - Yingchao Liu
AU  - Shuo Zhang
AU  - Guangji Zhang
PY  - 2026
DA  - 2026/11/03
JO  - Cancer Medicine
DO  - 10.1002/cam4.72381
UR  - https://doi.org/10.1002/cam4.72381
AB  - 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.
SN  - 2045-7634
ER  -