Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

doi:10.4251/wjgo.v16.i4.1514

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Apr 15, 2024 (publication date) through Feb 26, 2026

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1514-1531
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1514

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

Yong Pan, Yi-Ru Zhang, Ling-Yun Wang, Li-Na Wu, Ying-Qiu Ma, Zhou Fang, Shi-Bo Li

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 by the 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.

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
Processing time: 138 Days and 11 Hours

ARTICLE HIGHLIGHTS

Research background

Hepatocellular carcinoma (HCC) is a tumor with multi-etiology and multi-pathway involvement, and it is characterized by a low 5- year survival rate. Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in HCC. Nevertheless, the complexity and behavioral features of the ceRNA network in HCC are not fully elucidated.

Research motivation

To construct a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network in HCC.

Research objectives

To establish a CDKN2A-related ceRNA network in HCC and investigate the effect of the ceRNA on the prognosis of HCC.

Research methods

TCGA database, GEO database, cBioPortal database, lncBasev.3 database, miRDB database, Targetscan database, lncATLAS database, principal component analysis, The Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes pathway, meta-analysis, Kaplan-Meier plotter, nomogram, calibration curve, univariate and multivariate Cox regression, Spearman correlation coefficient, GSCALite database, UALCAN database, DiseaseMeth version 2.0 database, MEXPRESS database, TIMER database, CTD database, and PubChem database were used in this study.

Research results

CDKN2A was frequently mutated and deleted in and participated in cell cycle pathways in HCC. 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 for HCC patients. GAS5 expression was correlated with methylation level, immune infiltration, and the expression of three immune checkpoint genes in HCC.

Research conclusions

The CDKN2A-related ceRNA network-GAS5/miR-25-3p/SOX11 was successfully established and GAS5 was an independent prognostic indicator for HCC patients.

Research perspectives

The CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, regulating GAS5 expression might be an effective therapeutic strategy in inducing immune infiltration and immunotherapy for HCC.