Identification of UPB1 as a tumor suppressor associated with immune infiltration in cholangiocarcinoma

doi:10.3748/wjg.123490

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2027. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jan 7, 2027; 33(1): 123490
Published online Jan 7, 2027. doi: 10.3748/wjg.123490

Identification of UPB1 as a tumor suppressor associated with immune infiltration in cholangiocarcinoma

Zhong-Hai Sun, Bi-Cheng Zeng, Jia Sun, Bing-Lu Li, Zu-Yi Ma

Zhong-Hai Sun, Department of General Surgery, Sanshui Hospital, Zhujiang Hospital of Southern Medical University, Foshan 528000, Guangdong Province, China

Bi-Cheng Zeng, Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Jinan University (Dongguan Eastern Central Hospital), Dongguan 523000, Guangdong Province, China

Jia Sun, Bing-Lu Li, Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China

Zu-Yi Ma, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510000, Guangdong, China

Co-first authors: Zhong-Hai Sun and Bi-Cheng Zeng.

Co-corresponding authors: Bing-Lu Li and Zu-Yi Ma.

Author contributions: Sun ZH and Zeng BC contributed to conceptualization, methodology, original draft preparation, review and editing; Sun J contributed to data curation, visualization, investigation; Li BL and Ma ZY contributed to conceptualization, reviewing and editing, project administration, funding acquisition; Sun ZH and Zeng BC contributed equally to this work and should be considered co-first authors; Li BL and Ma ZY contributed equally to this work and should be considered co-corresponding authors; all authors have read and approved the final manuscript.

AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.

Supported by Scientific Research Promotion Program for Clinical Medicine, No. 2025CMFA08; Beijing Bethune Charitable Foundation, No. GDZL040; the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation, No. GZC20251430; and Sun Yat-sen Pilot Scientific Research Fund, No. YXQH202608.

Institutional review board statement: The study was approved by the Ethics Association of Peking Union Medical College Hospital (approval No. I-23PJ274).

Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Welfare and Ethics Committee of Peking Union Medical College Hospital (approval No. XHDW-2024-32).

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: RNA-sequencing data can be downloaded from TCGA (https://portal.gdc.cancer.gov/repository) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Other data that support the findings including technical appendix, statistical code, and dataset are available from the corresponding author at 13076335286@163.com upon reasonable request.

Corresponding author: Zu-Yi Ma, MD, Doctor, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, No. 107 Yanjiang West Road, Yuexiu District, Guangzhou 510000, Guangdong Province, China. 13076335286@163.com

Received: May 20, 2026
Revised: June 15, 2026
Accepted: July 2, 2026
Published online: January 7, 2027
Processing time: 173 Days and 19.7 Hours

Abstract

BACKGROUND

Cholangiocarcinoma (CCA) remains one of the most aggressive malignancies within the digestive tract, and identifying novel biomarkers and therapeutic targets is essential to improve patient survival. Recent studies have highlighted UPB1 as a predictive biomarker across multiple tumor types, but its biological involvement in CCA development and progression remains unclear.

AIM

To clarify the expression and prognostic value of UPB1 in CCA, its biological functions in tumor growth and immune infiltration.

METHODS

A combination of bioinformatics analyses and clinical data evaluation was applied to investigate UPB1 expression in CCA. Functional assays in cell models and xenograft mouse experiments were carried out to assess the influence of UPB1 on CCA growth. Co-culture assays were utilized to examine how UPB1 expression influences tumor immune infiltration.

RESULTS

Reduced UPB1 expression in CCA was correlated with unfavorable clinical manifestations and poor survival outcomes. In vitro studies demonstrated that UPB1 overexpression enhanced apoptosis and triggered G1/S cell cycle arrest in CCA cells. Reduced expression of BCL-2 and BIRC5, as well as down-regulation of CDK2 and CCNA2, were observed in UPB1 overexpressing cells. In vivo experiments further confirmed that UPB1 exerts a moderate tumor-suppressive effect on CCA xenograft development. Moreover, UPB1 expression showed a positive correlation with tumor-infiltrating lymphocytes, and in vitro co-culture assays suggested that UPB1 overexpression upregulated T-cell activation related transcripts and increased the release of immune factors.

CONCLUSION

UPB1 functions as a tumor suppressor in CCA and is associated with tumor immune infiltration. These results deepen understanding of CCA biology and highlight UPB1 as a promising therapeutic candidate.

Keywords: UPB1; Cholangiocarcinoma; Tumor suppressor; Immune infiltration; Cell cycle; Apoptosis

Core Tip: This study identifies UPB1 as a tumor-suppressor in cholangiocarcinoma (CCA). The expression of UPB1 is downregulated in CCA and correlates with adverse clinical features and worse survival. UPB1 overexpression enhances cell apoptosis and triggers G1/S phase arrest. UPB1 expression shows a positive correlation with tumor-infiltrating lymphocytes, and UPB1 overexpression promotes T-cell activation and immune factor release. UPB1 represents a novel prognostic biomarker and a candidate for further investigation in CCA.