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Copyright: ©Author(s) 2026. 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. Jul 14, 2026; 32(26): 119574
Published online Jul 14, 2026. doi: 10.3748/wjg.v32.i26.119574
High cyclin-dependent kinase 5 expression promotes tumor progression in gastric neuroendocrine carcinoma
Yu-Qin Sun, Jie Su, Kai-Ning Ye, Qiu-Xian Chen, En-Zhou Kang, Chen-Bin Lv, Ming-Qiao Lian, Wei-Ming Zeng, Yong-Bin Zhang, Li-Sheng Cai
Yu-Qin Sun, Qiu-Xian Chen, Chen-Bin Lv, Ming-Qiao Lian, Wei-Ming Zeng, Yong-Bin Zhang, Li-Sheng Cai, Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
Jie Su, Department of Ultrasonography, Zhangpu Hospital, Zhangzhou 363000, Fujian Province, China
Kai-Ning Ye, En-Zhou Kang, Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
Co-first authors: Yu-Qin Sun and Jie Su.
Author contributions: Sun YQ and Su J made equal contributions as co-first authors; Sun YQ, Su J, and Cai LS contributed to concept and design, drafting of the manuscript, and supervision; Ye KN, Chen QX, Kang EZ, Lv CB, Lian MQ, Zeng WM, and Zhang YB contributed to acquisition, analysis, or interpretation of data; Sun YQ, Su J, Zhang YB, and Zeng WM contributed to statistical analysis; Sun YQ, Su J, Ye KN, and Cai LS contributed to administrative, technical, or material support. All authors approved the final version to publish.
AI contribution statement: This article was translated using DeepL.
Supported by Natural Science Foundation of Fujian Province, No. 2025J011630; and the Climbing Fund of PhD Workstation, Zhangzhou Affiliated Hospital of Fujian Medical University, No. PDA202101.
Institutional review board statement: The study was approved by the Ethics Committee of the Zhangzhou Affiliated Hospital of Fujian Medical University, No.2026 LWB036.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Li-Sheng Cai, Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59 West Shengli Road, Zhangzhou 363000, Fujian Province, China. wxccls2024@163.com
Received: February 2, 2026
Revised: February 23, 2026
Accepted: March 23, 2026
Published online: July 14, 2026
Processing time: 146 Days and 15.6 Hours
Abstract
BACKGROUND

The function of cyclin-dependent kinase 5 (CDK5) in gastric neuroendocrine carcinoma (GNEC) is not yet fully understood.

AIM

To investigate the expression and function of CDK5 in GNEC.

METHODS

Immunohistochemistry was performed to measure CDK5, programmed death ligand-1, human epidermal growth factor receptor 2 (HER2), DNA mismatch repair, and Ki-67 antigen levels in paraffin-embedded samples. Epstein-Barr virus was detected via in situ hybridization, and HER2 was further analyzed with fluorescence in situ hybridization. The association between CDK5 expression, clinicopathological features, and patient outcomes was analyzed using univariate and multivariate statistics. CDK5’s role in GNEC was investigated through cell proliferation and colony formation assays.

RESULTS

This study included 65 patients diagnosed with GNEC, of whom 39 (60.0%) demonstrated elevated CDK5 expression and 26 (40.0%) exhibited reduced CDK5 expression. The observed expression pattern significantly correlated with tumor size and tumor-node-metastasis staging. Survival analyses indicated that patients with elevated CDK5 expression had lower overall survival and disease-free survival rates. Multivariate analysis further identified CDK5 as an independent prognostic risk factor for GNEC (hazard ratio = 2.13, 95% confidence interval: 1.03-4.41, P = 0.041). Additional analyses revealed a correlation between high CDK5 expression and increased Ki-67 indices, although no significant associations were found with programmed death ligand-1, HER2, Epstein-Barr virus, or mismatch repair status. Elevated CDK5 expression was also detected in GNEC cell lines ECC10 and ECC12. The knockdown of CDK5 significantly reduced the clonogenic and proliferative capacity of GNEC cells, whereas CDK5 overexpression did not significantly affect clonogenicity or cell proliferation.

CONCLUSION

These findings indicate that CDK5 is an independent prognostic risk factor and may play a crucial role in the proliferation of GNEC cells.

Keywords: Cyclin-dependent kinase 5; Gastric neuroendocrine carcinoma; Cell proliferation; Human epidermal growth factor receptor 2; Survival

Core Tip: This study aims to investigate the expression and function of cyclin-dependent kinase 5 (CDK5) in gastric neuroendocrine carcinoma (GNEC). The findings indicate that patients with elevated CDK5 expression in GNEC have a poor prognosis. Furthermore, CDK5 is identified as an independent prognostic risk factor and may play a critical role in the proliferation of GNEC.

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