Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3082-3096
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3082
BCAR3 and BCAR3-related competing endogenous RNA expression in hepatocellular carcinoma and their prognostic value
Hui-Qin Shi, Shu Huang, Xin-Yue Ma, Zhen-Ju Tan, Rui Luo, Bei Luo, Wei Zhang, Lei Shi, Xiao-Lin Zhong, Mu-Han Lü, Xia Chen, Xiao-Wei Tang
Hui-Qin Shi, Xin-Yue Ma, Zhen-Ju Tan, Rui Luo, Bei Luo, Wei Zhang, Lei Shi, Xiao-Lin Zhong, Mu-Han Lü, Xiao-Wei Tang, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
Shu Huang, Department of Gastroenterology, The People’s Hospital of Lianshui, Huaian 223499, Jiangsu Province, China
Shu Huang, Department of Gastroenterology, Lianshui People’ Hospital of Kangda College Affiliated to Nanjing Medical University, Huaian 223499, Jiangsu Province, China
Xia Chen, Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Co-first authors: Hui-Qin Shi and Shu Huang.
Co-corresponding authors: Xia Chen and Xiao-Wei Tang.
Author contributions: Tang XW was responsible for the design and conception of the research; Shi HQ and Huang S completed the writing and key revisions of the manuscript together; Ma XY, Tan ZJ, Zhang W, Shi L, Luo R, Luo B, Lü MH and Zhong XL jointly completed the data collection and analysis of the manuscript; Chen X and Tang XW completed the final revision and approval of the manuscript. All authors were involved in the critical review of the results and have contributed to read and approved the final manuscript. Shi HQ and Huang S contributed equally to this work as co-first authors. Chen X and Tang XW contributed to this work as co-corresponding authors. The reasons for designating Chen X and Tang XW as co-corresponding authors are threefold. First, the research was performed as a collaborative effort, and the designation of co-corresponding authors authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. This also ensures effective communication and management of post-submission matters, ultimately enhancing the paper's quality and reliability. Second, the overall research team encompassed authors with a variety of expertise and skills from different fields, and the designation of co-corresponding authors best reflects this diversity. This also promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives. Third, Chen X and Tang XW contributed efforts of equal substance throughout the research process. The choice of these researchers as co-corresponding authors acknowledges and respects this equal contribution, while recognizing the spirit of teamwork and collaboration of this study. In summary, we believe that designating Chen X and Tang XW as co-corresponding authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.
Conflict-of-interest statement: There are no conflicts of interest to declare.
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: Xiao-Wei Tang, MD, PhD, Associate Professor, Postdoc, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang Region, Luzhou 646000, Sichuan Province, China. solitude5834@hotmail.com
Received: April 8, 2024
Revised: May 23, 2024
Accepted: June 13, 2024
Published online: July 15, 2024
Processing time: 95 Days and 1.9 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is a malignant tumor that has a high incidence and mortality worldwide. Despite extensive studies, the detailed molecular mechanism of HCC development remains unclear. Studies have shown that the occurrence and development of HCC are closely related to abnormal gene expression. BCAR3 has been shown to be overexpressed in a variety of malignant tumors. However, the role of BCAR3 in HCC remains unclear.

AIM

To investigate the expression of BCAR3 and BCAR3-related competing endogenous RNAs (ceRNAs) in HCC and their clinical significance, in order to provide new ideas for the diagnosis and treatment of HCC.

METHODS

The data of HCC were obtained from the Cancer Genome Atlas database and The Genotype Tissue Expression, including transcriptome data and clinical information. Multiple common databases, including UALCAN, Timer 2.0, cBioPortal, LinkedOmics, starBase, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were used to analyse the expression of BCAR3, prognostic value, genetic alteration, co-expressed genes, differentially expressed genes, BCAR3 gene-related ceRNAs and functional enrichment analysis in HCC patients. Kaplan-Meier analysis, univariate and multivariate Cox regression analysis were used to analyze survival prognosis and the Spearman test was used to measure correlations between BCAR3 and immune functions. And R language package was used to analyze the correlation between BCAR3 and immune invasion of HCC.

RESULTS

Our study indicated that BCAR3 was differentially expressed in various tumor tissues. The over-expression of BCAR3 gene was an unfavorable prognostic indicator for HCC patients, and associated with unfavorable cytogenetic risk and gene mutations. Moreover, most immune cells were positively correlated with BCAR3 (P < 0.05). According to the results of functional enrichment analysis, BCAR3 was involved in the positive regulation of epidermal growth factor receptor signaling pathway and ERBB signaling pathway, and was related to DNA replication and GTPase regulator activity. Finally, our study found that based on RAB30-DT and miR-19b-3p pathways, targeting BCAR3 might promote the occurrence and development of HCC.

CONCLUSION

Collectively, this study indicated that the BCAR3 gene was involved in the occurrence and development of HCC, and it might be a new biomarker and therapeutic target for HCC, but the specific mechanism remains to be further verified.

Keywords: Hepatocellular carcinoma, Breast cancer anti-estrogen-resistant protein 3, Bioinformatics, Prognosis, Immunoassay

Core Tip:BCAR3 gene was over-expressed in a variety of malignant tumors, and its high expression was significantly associated with poor prognosis of cancer patients. In hepatocellular carcinoma (HCC), the expression of BCAR3 was observably higher in cancer tissues than in normal tissues, and the expression level was higher in HCC tissues with TP53 mutation compared to those without. BCAR3 was positively correlated with a variety of immune cells in HCC tissues, and might play an important role in the immune micro-environment of tumors. In addition, the BCAR3/miR-19b-3p/RAB30-DT competing endogenous RNA regulatory axis may be involved in the development of HCC.