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TIPE2 serves as a favorable prognostic biomarker and suppresses cholangiocarcinoma progression by targeting RAC1-mediated integrin αvβ6 trafficking
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  • Published: 29 January 2026

TIPE2 serves as a favorable prognostic biomarker and suppresses cholangiocarcinoma progression by targeting RAC1-mediated integrin αvβ6 trafficking

  • Shasha Wang1 na1,
  • Wenyu Jia2 na1,
  • Yuqi Sun3,
  • Cheng Meng3,
  • Jun Niu4 &
  • …
  • Zequn Li3 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biomarkers
  • Gastrointestinal cancer
  • Hepatology
  • Tumour biomarkers

Abstract

Tumor necrosis factor-α-induced protein-8 (TNFAIP8/TIPE) like-2 (TIPE2), a critical member of the TIPE protein family, has been characterized as a tumor suppressor across multiple malignancies. Its functional significance in cholangiocarcinoma pathogenesis remains poorly defined. To address this knowledge gap, we established a discovery cohort of 218 cholangiocarcinoma patients and an independent validation cohort of 95 cases. The expression of TIPE2 was explored via immunohistochemistry (IHC). The correlation between patients’ clinical parameters including overall survival and TIPE2 expression were evaluated. A nomogram including TIPE2 expression was also constructed and validated to for prognostic prediction. The effect and related mechanisms of TIPE2 on the malignant behaviors of cholangiocarcinoma was investigated both in vitro, in silico, and in vivo. The two cohorts demonstrated that TIPE2 expression was decreased in cholangiocarcinoma tissues, and TIPE2 expression was closely related with tumor stage and the prognosis of cholangiocarcinoma patients. Nomogram including TIPE2 expression could predict the prognosis of cholangiocarcinoma patients effectively. TIPE2 suppressed the proliferation, migration and invasion capacities of cholangiocarcinoma cells, and inhibited tumor growth in vivo. Mechanistically, TIPE2 suppressed the trafficking of integrin αvβ6 via targeting RAC1, which subsequently suppressed the progression of cholangiocarcinoma. Through comprehensive clinical cohorts and functional investigations, the present study identified TIPE2 as a clinically significant prognostic biomarker and revealed its potential role in regulating integrin-mediated oncogenic processes in cholangiocarcinoma. Therapeutic enhancement of TIPE2 expression emerges as a promising precision medicine strategy for cholangiocarcinoma management.

Data availability

All the related data are available upon request by contacting with the corresponding author.

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Funding

This work was supported by Young Talent of Lifting engineering for Science and Technology in Shandong, China (No. SDAST2024QTA032), Wu Jieping Medical Foundation Clinical Research Special Fund (No. 320.6750.2024–17-41).

Author information

Author notes

  1. Shasha Wang and Wenyu Jia contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China

    Shasha Wang

  2. Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, 266071, Shandong, China

    Wenyu Jia

  3. Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China

    Yuqi Sun, Cheng Meng & Zequn Li

  4. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China

    Jun Niu

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Contributions

ZL designed the study, acquired funding and edited the manuscript, SW and WJ performed the experiments, analyzed the results and wrote the original draft, YS and CM collected and examined the data, JN contributed to the establishment of two cohorts and reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zequn Li.

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Wang, S., Jia, W., Sun, Y. et al. TIPE2 serves as a favorable prognostic biomarker and suppresses cholangiocarcinoma progression by targeting RAC1-mediated integrin αvβ6 trafficking. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37540-9

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  • Received: 21 June 2025

  • Accepted: 22 January 2026

  • Published: 29 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-37540-9

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Keywords

  • Cholangiocarcinoma
  • TIPE2
  • Biomarker
  • Integrin αvβ6
  • RAC1
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