Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2024; 16(2): 436-457
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.436
Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer
Yao Rong, Ming-Zheng Tang, Song-Hua Liu, Xiao-Feng Li, Hui Cai
Yao Rong, Ming-Zheng Tang, Song-Hua Liu, Xiao-Feng Li, First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Yao Rong, Ming-Zheng Tang, Song-Hua Liu, Hui Cai, General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Yao Rong, Ming-Zheng Tang, Hui Cai, Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Yao Rong, Ming-Zheng Tang, Hui Cai, NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Co-first authors: Yao Rong and Ming-Zheng Tang.
Author contributions: Rong Y and Tang MZ were co-first authors. Rong Y, Tang MZ, and Cai H conceived the study; Rong Y wrote the manuscript; Rong Y and Tang MZ completed the methodology section, produced the images and tables, and completed the in vitro experiments; Liu SH collected the relevant data; Li XF analysed the data; Cai H reviewed the paper; and all authors read and approved the final draft.
Supported by 2021 Central-Guided Local Science and Technology Development Fund; National Key Research and Development Program, No. 2018YFC1311506; Gansu Provincial People’s Hospital Intramural Cultivation Key Project, No. 19SYPYA-1; and Lanzhou COVID-19 Prevention and Control Technology Research Project, No. 2020-XG-1.
Institutional review board statement: The research experiment only addresses the validation of cancer cell expression at the in vitro level, and does not involve human or animal related studies, therefore no Institutional Review Board approval form or document is applicable.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.
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:
Corresponding author: Hui Cai, PhD, Doctor, General Surgery Clinical Medical Center, Gansu Provincial Hospital, No. 204 Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, China.
Received: August 19, 2023
Peer-review started: August 19, 2023
First decision: December 5, 2023
Revised: December 13, 2023
Accepted: January 9, 2024
Article in press: January 9, 2024
Published online: February 15, 2024

A growing number of clinical examples suggest that coronavirus disease 2019 (COVID-19) appears to have an impact on the treatment of patients with liver cancer compared to the normal population, and the prevalence of COVID-19 is significantly higher in patients with liver cancer. However, this mechanism of action has not been clarified.


To investigate the disease relevance of COVID-19 in liver cancer.


Gene sets for COVID-19 (GSE180226) and liver cancer (GSE87630) were obtained from the Gene Expression Omnibus database. After identifying the common differentially expressed genes (DEGs) of COVID-19 and liver cancer, functional enrichment analysis, protein-protein interaction network construction and screening and analysis of hub genes were performed. Subsequently, the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.


Of 518 common DEGs were obtained by screening for functional analysis. Fifteen hub genes including aurora kinase B, cyclin B2, cell division cycle 20, cell division cycle associated 8, nucleolar and spindle associated protein 1, etc., were further identified from DEGs using the “cytoHubba” plugin. Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation, cell cycle and other functions, and they may serve as potential molecular markers for COVID-19 and liver cancer. Finally, we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.


Our study reveals a common pathogenesis of liver cancer and COVID-19. These common pathways and key genes may provide new ideas for further mechanistic studies.

Keywords: COVID-19, Liver cancer, Differentially expressed genes, Hub genes, Pathogenesis

Core Tip: In this study, bioinformatics analysis was used as a bridge to correlate coronavirus disease 2019 (COVID-19) with liver cancer to explore the correlation and common molecular mechanisms between the two. This study explored the common differentially expressed genes between COVID-19 and liver cancer, from which key hub genes were identified and analyzed for protein-protein interaction network topology as well as Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The expression of some of the hub genes in different liver cancer cells was specifically verified by quantitative reverse transcriptase polymerase chain reaction. Our study suggests that the pathogenic association and regulatory mechanism of COVID-19 with liver cancer may be due to the role of specific hub genes, such as PDZ binding kinase, targeting protein for xklp2, aurora kinase B, etc. and the mediation of P53 signaling pathway.