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
Abstract
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.

AIM

To explore the specific mechanism of action of SMARCA4 in HCC.

METHODS

Herein, the expression level of SMARCA4 as well as its association with HCC prognosis were evaluated using transcriptome profiling and clinical data of 18 different types of cancer collected from The Cancer Genome Atlas database. Furthermore, SMARCA4-high and -low groups were identified. Thereafter, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the function of SMARCA4, followed by construction of a SMARCA4-specific competing endogenous RNA (ceRNA) network using starBase database. The role of SMARCA4 in immunotherapy and its association with immune cells were assessed using correlation analysis.

RESULTS

It was observed that SMARCA4 was overexpressed and negatively correlated with prognosis in HCC. Further, SMARCA4 expression was positively associated with tumor mutational burden, microsatellite stability, and immunotherapy efficacy. The SNHG3/THUMP3-AS1-miR-139-5p-SMARCA4 ceRNA network was established and could be assumed to serve as a stimulatory mechanism in HCC.

CONCLUSION

The findings of this study demonstrated that SMARCA4 plays a significant role in progression and immune infiltration in HCC. Moreover, a ceRNA network was detected, which was found to be correlated with poor prognosis in HCC. The findings of this study could contribute towards the identification of predictive markers for immunotherapy and a novel mechanism of action for HCC treatment.

Keywords: Hepatocellular carcinoma, SMARCA4, Prognosis, Immune infiltration, Competing endogenous RNA

Core Tip: 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. To date, 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. 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.