Molecular Traces of Gastric Cancer in Saliva: From Tissue Signatures to Salivary SLC5A5 as a Potential Biomarker

Journal article

Background: Early detection of gastric cancer (GC) and reliable risk stratification for metachronous gastric lesions (MGLs) remain societal and clinical challenges, particularly in intermediate risk populations. Non‐invasive approaches such as saliva‐based biomarkers could complement current strategies. The aim of this study was to identify and validate a tissue‐based gene expression signature for early gastric lesions, explore its potential for MGL prediction, and assess its detectability in saliva. Methods: Three studies were conducted: (1) a retrospective case control study to identify (RNA sequencing with machine learning) and validate (reverse transcription [RT] quantitative polymerase chain reaction [qPCR]) a gene expression signature for early gastric cancer using formalin‐fixed paraffin‐embedded (FFPE) samples, (2) a retrospective longitudinal study evaluating the ability of the signature to stratify MGL risk, and (3) a prospective study testing the signature in saliva using droplet digital (dd)PCR in patients with gastric lesions and endoscopy‐confirmed controls. Results: A six‐gene tissue‐based expression signature (ADAMTSL1, CCNA2, HSP90AB1, HSPD1, PSAPL1, and SLC5A5) robustly discriminated early gastric lesions from non‐tumor mucosa (area under the curve (AUC) = 0.96 and 95% confidence interval [CI]: 0.94–0.99). Models tailored for MGL prediction, incorporating clinical variables, achieved moderate performance (AUC = 0.74 and 95% CI: 0.59–0.88). In saliva, only the SLC5A5 gene showed consistent dysregulation. When combined with age and sex, the model reached an AUC of 0.78 (95% CI: 0.69–0.88) for the non‐invasive detection of early GC, with a positive predictive value of 0.69 and negative predictive value of 0.81. Conclusion: This study presents a validated tissue‐based gene signature for early GC detection and exploratory MGL risk stratification. Salivary SLC5A5 shows potential as a non‐invasive biomarker, though its utility requires further validation in dedicated saliva‐based studies.

Authors: Lopes, C; Brandão, A; Vavoulis, D; Paulino, S; Costa, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: United European Gastroenterology Journal
• Volume: 14
• Issue: 4
• Article number: e70221
• Publication date: 2026-05-23
• Acceptance date: 2026-04-10
• DOI: 10.1002/ueg2.70221
• EISSN: 2050-6414
• ISSN: 2050-6406
• Language: English
• Keywords: gastric lesions; biomarkers; personalized medicine; liquid biopsy