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Updated: Aug 6, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Hepatic origin of increased serum TFF3 in gastric cancer bearing subjects
Komei Kuge1,2, Junko Mukoyama3, Yoshimi Yasukawa1,4
1Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Background:
Serum trefoil factor 3 (TFF3) has emerged as a promising biomarker for gastric cancer; however, its biological origin remains unclear.
Methods:
Gastric cancer was induced by Helicobacter pylori infection combined with N-methyl-N-nitrosourea (MNU), whereas a rat model was established using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone. Serum TFF levels were measured by ELISA. Organ-specific TFF3 expression, cytokine profiles, STAT3 activation, and epigenetic regulation were analyzed using RT-PCR, immunohistochemistry, multiplex assays, Western blotting, and ChIP-qPCR.
Results:
Serum TFF1-3 levels were significantly elevated in gastric cancer-bearing mice, with TFF3 showing robust diagnostic performance. In rats, serum TFF3 levels remained unchanged after total gastrectomy. TFF3 expression was selectively upregulated in the liver, accompanied by STAT3 activation. Gastric IL-6 expression was increased, suggesting portal-mediated signaling to the liver. ChIP-qPCR demonstrated sustained enrichment of H3K27ac at the TFF3 locus following IL-6 stimulation.
Conclusions:
Increased serum TFF3 in gastric cancer originates from the liver and is associated with IL-6-STAT3 signaling. Persistent elevation after gastrectomy may be explained by epigenetic activation, supporting the biological basis of TFF3 as a surrogate marker.
