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World J Hepatol. Mar 27, 2026; 18(3): 117134
Published online Mar 27, 2026. doi: 10.4254/wjh.v18.i3.117134
Published online Mar 27, 2026. doi: 10.4254/wjh.v18.i3.117134
Overexpression and clinicopathological significance of cullin-2 in hepatocellular carcinoma progression
Pan Tang, Qiu-Hong Nong, Kun-Hua Xiong, Huan-Huan Tang, Bei-Bei Huang, Guang-Lei Huang, Qi Li, Shi-Pei He, Gang Chen, Zhen-Bo Feng, Jian-Di Li, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Pan Tang and Qiu-Hong Nong.
Co-corresponding authors: Zhen-Bo Feng and Jian-Di Li.
Author contributions: Tang P, Nong QH, Feng ZB, and Li JD contributed to the conception and design of the study; Tang P, Nong QH, Xiong KH, Tang HH, Huang BB, Huang GL, Li Q, and He SP contributed to the acquisition, analysis, or interpretation of data; Feng ZB, Li JD, and Chen G contributed to the supervision, editing of the content, and writing of the final version of the manuscript; all authors have read and approved the final manuscript. Tang P and Nong QH contributed equally to this work as co-first authors. We designate Feng ZB and Li JD as joint corresponding authors for the following reasons: As the graduate supervisor of the first author, Feng ZB led the entire process of the study, including overall project design, selection of key experimental indicators, guidance on core experimental operations, and systematic literature research, providing important academic leadership and resource support for the smooth implementation of the research. As the research mentor, Li JD offered direct and detailed guidance in key late-stage research steps such as data calculation, advanced statistical analysis, scientific figure preparation, and in-depth interpretation of experimental results, playing an indispensable role in ensuring the rigor of the research conclusions and the quality of result presentation. Both supervisors made equally significant contributions to this study from different stages and dimensions, and bear core responsibility for the integrity and scientific validity of the research.
Supported by National Natural Science Foundation of China, No. 82260581; Innovation Project of Guangxi Graduate Education, No. JGY2023068; Guangxi Medical University “Four New” Project, No. SX202403; Guangxi Medical University Special Project on Educational and Teaching Reform for Clinical Disciplines, No. 2025LCJG02; Guangxi Medical University Digital Textbook Construction Project, No. Gxmuszjc2515; China Undergraduate Innovation and Entrepreneurship Training Program, No. 202510598040; and Future Academic Star of Guangxi Medical University, No. WLXSZX25B079.
Institutional review board statement: This study was reviewed and approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (Approval No. 2022-KT-NSFC-127). All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data sharing statement: The data supporting this study can be obtained from the corresponding author upon reasonable request.
Corresponding author: Jian-Di Li, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. jiandi_li_gxmu@163.com
Received: December 1, 2025
Revised: December 23, 2025
Accepted: February 4, 2026
Published online: March 27, 2026
Processing time: 116 Days and 21.1 Hours
Revised: December 23, 2025
Accepted: February 4, 2026
Published online: March 27, 2026
Processing time: 116 Days and 21.1 Hours
Core Tip
Core Tip: Cullin-2 (CUL2) is highly expressed in mRNA and protein levels in hepatocellular carcinoma (HCC). Multicenter analysis (n = 5204) confirmed its high expression (standardized mean difference = 0.70) and diagnostic value (area under the curve = 0.78). The overall survival of patients with high expression was shortened by about 4.1 years. Functional enrichment showed that it was associated with E2F, G2/M and MYC pathways and promoted cell cycle progression. Knockout of CUL2 significantly inhibited the growth of HCC cells, indicating that CUL2 drives HCC progression through proliferation and migration.