Hepatic origin of increased serum TFF3 in gastric cancer bearing subjects.

IF 6.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2026-09-01 Epub Date: 2026-07-20 DOI:10.1007/s10120-026-01782-3

Komei Kuge, Junko Mukohyama, Yoshimi Yasukawa, Yuko Ishibashi, Hiroki Masuda, Tomohiko Yasuda, Yasukazu Ohmoto, Hideyuki Takeshima, Akihisa Matsuda, Hiroshi Yoshida, Yasuyuki Seto, James R Goldenring, Toshikazu Ushijima, Sachiyo Nomura

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引用次数: 0

Abstract

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.

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胃癌患者血清TFF3升高的肝脏来源。

背景：血清三叶因子3 （TFF3）已成为一种有前景的胃癌生物标志物；然而，其生物学起源仍不清楚。方法：采用幽门螺杆菌联合n -甲基-n -亚硝基胍（MNU）诱导胃癌，单独使用n -甲基-n '-硝基-n -亚硝基胍（MNNG）建立大鼠模型。ELISA法测定血清TFF水平。使用RT-PCR、免疫组织化学、多重检测、Western blotting和ChIP-qPCR分析器官特异性TFF3表达、细胞因子谱、STAT3激活和表观遗传调控。结果：胃癌小鼠血清TFF1-3水平显著升高，TFF3具有较强的诊断作用。大鼠全胃切除术后血清TFF3水平保持不变。肝脏中TFF3表达选择性上调，同时伴有STAT3激活。胃IL-6表达增加，提示经门静脉介导的信号传导至肝脏。ChIP-qPCR显示，在IL-6刺激后，H3K27ac在TFF3位点持续富集。结论：胃癌患者血清TFF3升高源于肝脏，与IL-6-STAT3信号通路相关。胃切除术后持续升高可解释为表观遗传激活，支持TFF3作为替代标志物的生物学基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.