Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3069-3081
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3069
Prognostic significance of exportin-5 in hepatocellular carcinoma
Hao Li, Fei Li, Bo-Shen Wang, Bao-Li Zhu
Hao Li, Fei Li, Bo-Shen Wang, Bao-Li Zhu, Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing 210000, Jiangsu Province, China
Hao Li, Fei Li, Bo-Shen Wang, Bao-Li Zhu, Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210000, Jiangsu Province, China
Bao-Li Zhu, Committee, Jiangsu Preventive Medical Association, Nanjing 210000, Jiangsu Province, China
Bao-Li Zhu, Center for Global Health, Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
Bao-Li Zhu, Public Health Sector, Jiangsu Province Engineering Research Center Jiangsu Province Engineering Research Center of Health Emergency, Nanjing 210000, Jiangsu Province, China
Co-first authors: Hao Li and Fei Li.
Co-corresponding authors: Bo-Shen Wang and Bao-Li Zhu.
Author contributions: Li H and Wang BS designed the research study; Li H, Li F, and Wang BS performed the research; Zhu BL contributed new resources and supervision; Li H and Li F analyzed the data and wrote the manuscript; and all authors have read and approved the final manuscript. Li H and Li F contributed equally to this work as co-first authors; Wang BS and Zhu BL contributed equally to this work as co-corresponding authors. The reasons for designating Wang BS and Zhu BL as co-corresponding authors are that they provide comparable research resources and writing guidance.
Supported by the Scientific Research Project of Jiangsu Health Committee, No. M2022083; Natural Science Foundation of Jiangsu Province, No. BK20230742; Open Project of Key Laboratory of Environmental Medicine Engineering of Ministry of Education, No. 2022EME001; and Laboratory of Jiangsu Provincial Medical Key Discipline, No. ZDXK202249.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bao-Li Zhu, Doctor, Associate Chief Physician, Chairman, Professor, Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, No. 172 Jiangsu Road, Nanjing 210000, Jiangsu Province, China. zhublcdc@sina.com
Received: April 5, 2024
Revised: May 5, 2024
Accepted: May 22, 2024
Published online: July 15, 2024
Processing time: 97 Days and 19.6 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. As liver cancer often presents no noticeable symptoms in its early stages, most patients are diagnosed at an advanced stage, complicating treatment. Therefore, the identification of new biomarkers is crucial for the early detection and treatment of HCC. Research on exportin-5 (XPO5) could offer new avenues for early diagnosis and improve treatment strategies.

AIM

To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker.

METHODS

This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas, TIMER, and International Cancer Genome Consortium databases, correlating it with clinical profiles and disease progression. We performed in vitro experiments to examine the effect of XPO5 on liver cell growth. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were used to elucidate the biological roles and signaling pathways. We also evaluated XPO5’s impact on immune cell infiltration and validated its prognostic potential using machine learning.

RESULTS

XPO5 was significantly upregulated in HCC tissues, correlating with tumor grade, T-stage, and overall survival, indicating poor prognosis. Enrichment analyses linked high XPO5 expression with tumor immunity, particularly CD4 T cell memory activation and macrophage M0 infiltration. Drug sensitivity tests identified potential therapeutic agents such as MG-132, paclitaxel, and WH-4-023. Overexpression of XPO5 in HCC cells, compared to normal liver cells, was confirmed by western blotting and quantitative real-time polymerase chain reaction. The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis. Among the various machine learning algorithms, the C5.0 decision tree algorithm achieved accuracy rates of 95.5% in the training set and 92.0% in the validation set.

CONCLUSION

Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.

Keywords: Exportin-5 expression; Hepatocellular carcinoma; Prognostic biomarker; In vitro experiments; Bioinformatic analysis

Core Tip: This study reveals the pivotal role of exportin-5 (XPO5), a miRNA transport protein, in the progression and prognosis of hepatocellular carcinoma (HCC). Bioinformatic databases and in vitro assays demonstrated that XPO5 expression was upregulated in HCC tissues, correlating with aggressive tumor features and poor patient outcomes. Furthermore, XPO5 levels influenced immune cell behavior, particularly in T cells and macrophages, suggesting its potential as a target for immunotherapy. This study suggests that XPO5 could be used as a biomarker for the prognosis of HCC and as a novel therapeutic target.