Evidence-Based Medicine
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 16, 2022; 10(29): 10501-10515
Published online Oct 16, 2022. doi: 10.12998/wjcc.v10.i29.10501
Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma
Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
Lei Zhang, Ting Sun, Xiao-Ye Wu, Department of Clinical Oncology, Jiaxing Second Hospital, Jiaxing 314000, Zhejiang Province, China
Fa-Ming Fei, Zhen-Zhen Gao, Department of Clinical Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
Author contributions: Zhang L and Sun T designed the research study; Wu XY performed the research; Gao ZZ and Fei FM contributed new reagents and analytic tools; Zhang L and Gao ZZ analyzed the data and wrote the manuscript; all authors have read and approve the final manuscript.
Conflict-of-interest statement: All authors declared they have not any competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Zhen-Zhen Gao, MD, PhD, Director, Department of Clinical Oncology, The Second Affiliated Hospital of Jiaxing University, No. 1518 Huancheng Road, Jiaxing 314000, Zhejiang Province, China. sarrah0112@163.com
Received: July 2, 2022
Peer-review started: July 2, 2022
First decision: August 1, 2022
Revised: August 14, 2022
Accepted: August 30, 2022
Article in press: August 30, 2022
Published online: October 16, 2022
Research background

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and the mortality rate continues to rise each year. SMARCA4 expression has been associated with poor prognosis in various types of cancer; however, the specific mechanism of action of SMARCA4 in HCC needs to be fully elucidated.

Research motivation

Only few studies have successfully elucidated the mechanism of action of SMARCA4 in the progression of HCC. In the present study, we aimed to establish a SMARCA4-related competing endogenous RNA (ceRNA) network by mapping and analyzing the transcription profiles of SMARCA4 in HCC.

Research objectives

To provide valuable insights regarding HCC occurrence and development.

Research methods

(1) Data sources and survival analysis; (2) Establishment of SMARCA4 related differentially expressed genes (DEGs) and delineation of functional enrichment analysis; (3) Prediction of miRNAs and lnRNAs upstream of SMARCA4; (4) Correlation of SMARCA4 and immune cells and the markers; and (5) The R packages used in this study included limma, reshape2, ggpubr, ggExtra, survival, survminer, and reshape2 whereas Cytoscape was used to establish the ceRNA network.

Research results

Pan-cancer expression levels of SMARCA4. Differential expression of SMARCA4 and its prognostic value in patients with HCC. Identification of DEGs and enrichment analysis between SMARCA4high and SMARCA4low patients. Identification of miRNAs upstream of SMARCA4. Detection and analysis of long noncoding RNAs (lncRNAs) upstream of hsa-miR-139-5p. Relationship between the expression levels of SMARCA4 and immune cell infiltration. Relationship between expression levels of SMARCA4 and biomarkers of immune cells.

Research conclusions

Herein, we demonstrated the overexpression of SMARCA4 in patients with HCC and in several immunotherapy-related pathways. Furthermore, an increased expression of SMARCA4 was found to be positively associated with immune cell infiltration, and a SMARCA4-specific ceRNA network was established, which was found to be involved in the progression of HCC.

Research perspectives

We observed the overexpression of SMARCA4 in different pathways. Additionally, the overexpression of SMARCA4 was correlated to an increased immune cell infiltration and an augmented sensitivity to immunotherapy. Furthermore, a novel SMARCA4 ceRNA network (SNHG3/THUMP3-AS1-miR-139-5p-SMARCA4) was established in this study. This study could contribute towards the identification of predictive markers for immunotherapy and a novel mechanism of action for HCC treatment.