Pan Y, Zhang YR, Wang LY, Wu LN, Ma YQ, Fang Z, Li SB. Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16(4): 1514-1531 [PMID: 38660664 DOI: 10.4251/wjgo.v16.i4.1514]
Corresponding Author of This Article
Shi-Bo Li, Doctor, Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, No. 739 Dingshen Road, Zhoushan 316021, Zhejiang Province, China. lsb0398@126.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Yong Pan, Yi-Ru Zhang, Ling-Yun Wang, Ying-Qiu Ma, Zhou Fang, Shi-Bo Li, Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, Zhoushan 316021, Zhejiang Province, China
Yi-Ru Zhang, Ling-Yun Wang, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Li-Na Wu, Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
Author contributions: Pan Y and Zhang YR initiated the study and organized it; Wang LY, Ma YQ, and Fang Z designed and carried out bioinformatics analyses, statistical analyses, and drew figures; Pan Y and Wu LN drafted the manuscript; Li SB contributed to the review and editing; all authors have read and agreed to the published version of the manuscript.
Supported bythe Zhejiang Province Major Science and Technology Project for Medicine and Health, No. WKJ-ZJ-2329.
Institutional review board statement: Our research is based on the Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) database and the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) database. All of these are open-access public databases. Thus, no institutional review board approval was required.
Informed consent statement: Patients were not required to give informed consent to the study because our research is based on the databases.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
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: Shi-Bo Li, Doctor, Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, No. 739 Dingshen Road, Zhoushan 316021, Zhejiang Province, China. lsb0398@126.com
Received: November 24, 2023 Peer-review started: November 24, 2023 First decision: January 12, 2024 Revised: January 16, 2024 Accepted: February 4, 2024 Article in press: February 4, 2024 Published online: April 15, 2024
Abstract
BACKGROUND
Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal.
AIM
To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.
METHODS
The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators.
RESULTS
CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained.
CONCLUSION
This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.
Core Tip: In this study, the mutation landscape, and molecular biological mechanisms of cyclin dependent kinase inhibitor 2A (CDKN2A) in hepatocellular carcinoma (HCC) was first explored, and a CDKN2A-related competitive endogenous RNA axis was constructed. We identified growth arrest specific 5 as an independent prognostic biomarker and established a prognostic nomogram model for HCC. Moreover, we analyzed its methylation level, immune infiltration, and targeted agents, which might be an independent prognostic biomarker and therapeutic target in HCC.
