Imanishi D, Nishikubo H, Ma D, Sano T, Fan C, Sakuma T, Yashiro M. Dual function of transforming growth factor beta 2 in the progression of gastric carcinoma. World J Biol Chem 2026; 17(3): 121664 [DOI: 10.4331/wjbc.121664]
Corresponding Author of This Article
Masakazu Yashiro, MD, PhD, Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 5458585, Japan. i21496f@omu.ac.jp
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Oncology
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research-article
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Imanishi D, Nishikubo H, Ma D, Sano T, Fan C, Sakuma T, Yashiro M. Dual function of transforming growth factor beta 2 in the progression of gastric carcinoma. World J Biol Chem 2026; 17(3): 121664 [DOI: 10.4331/wjbc.121664]
Daiki Imanishi, Hinano Nishikubo, Dongheng Ma, Tomoya Sano, Canfeng Fan, Takashi Sakuma, Masakazu Yashiro, Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka 5458585, Japan
Author contributions: Imanishi D performed the experiments of this study, interpreted the data and wrote the manuscript; Nishikubo H, Ma D, Sano T, and Fan C contributed to the immunohistochemical analysis; Sakuma T helped draft the manuscript; Yashiro M designed the experiments of this study, interpreted the data and edited the manuscript; and all authors thoroughly reviewed and endorsed the final manuscript.
AI contribution statement: AI tool were not used.
Supported by Grants-in-Aid for Scientific Research, No. 24K02525.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Osaka Metropolitan University, approval No. 2022-111, No. 924, and No. 2022-077.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Participants gave informed consent for data sharing.
Corresponding author: Masakazu Yashiro, MD, PhD, Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 5458585, Japan. i21496f@omu.ac.jp
Received: April 1, 2026 Revised: May 11, 2026 Accepted: June 8, 2026 Published online: September 5, 2026 Processing time: 157 Days and 14 Hours
Abstract
BACKGROUND
It has been reported that transforming growth factor beta (TGFβ) might play an important role for the development of various types of carcinomas. TGFβ is produced from not only cancer cells but also stromal cells such as fibroblasts. Controversial functions of TGFβ for tumor progression such as tumor suppression and progression has been widely recognized. TGFβ has 3 subtypes including TGFβ1, TGFβ2, and TGFβ3. The role of TGFβ1 and TGFβ3 for gastric carcinoma (GC) progression has been well-known, but that of TGFβ2 remains to be unknown.
AIM
To clarify the significance of TGFβ2 in the development of GC.
METHODS
Immunohistochemical analysis of GC was performed to clarify the clinical function of TGFβ2 on the progression of GC by evaluating TGFβ2 expression on both cancer cells and cancer-associated fibroblasts (CAFs) using 518 GC specimens.
RESULTS
High TGFβ2 expression in cancer cells was significantly correlated with T factor and stage, but not with vascular invasion and lymphatic invasion. In contrast, TGFβ2 expression on CAFs was significantly correlated with lymph node metastasis and vascular invasion, but not with the T factor. Five-year survival of patients with TGFβ2-high on cancer cells and -low on CAFs was significantly worse in compared to the other group These findings suggest that TGFβ2 might play differential roles between cancer cells and CAFs in the development of GC.
CONCLUSION
TGFβ2 on cancer cells might stimulates the cancer proliferation and invasion, but not TGFβ2 on CAFs. TGFβ2 high on cancer cells and low on CAF or others might be a promising prognostic factor for patients with GC.
Core Tip: The immunohistochemical analysis of gastric carcinoma (GC) was performed to clarify the clinical function of transforming growth factor beta 2 (TGFβ2) on the progression of GC. TGFβ2 expression on cancer-associated fibroblasts (CAFs) was significantly correlated with lymph node metastasis and vascular invasion, but not with the T factor. Five-year survival of patients with TGFβ2-high on cancer cells and -low on CAFs was significantly worse in compared to the other group TGFβ2 on cancer cells might stimulates the cancer proliferation and invasion, but not TGFβ2 on CAFs. TGFβ2 high on cancer cells and low on CAF or others might be a promising prognostic factor for patients with GC.
