Evidence-Based Medicine
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2023; 15(7): 1295-1310
Published online Jul 15, 2023. doi: 10.4251/wjgo.v15.i7.1295
Comprehensive bioinformatic analysis of mind bomb 1 gene in stomach adenocarcinoma
Di Wang, Qi-Hong Wang, Ting Luo, Wen Jia, Jing Wang
Di Wang, Qi-Hong Wang, Ting Luo, Wen Jia, Jing Wang, Department of Digestive Endoscopy, The General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
Di Wang, Qi-Hong Wang, Ting Luo, Postgraduate College, China Medical University, Shenyang 110840, Liaoning Province, China
Author contributions: Wang J contributed to conceptualization; Wang D wrote the paper; Wang QH, Luo T, and Jia W collected and analyzed data.
Supported by the Science and Technology Program of Liaoning Province, No. 2021-MS-040.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
PRISMA 2009 Checklist statement: We 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: Jing Wang, MS, Deputy Director, Department of Digestive Endoscopy, The General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenhe District, Shenyang 110840, Liaoning Province, China. 13309882063@163.com
Received: February 27, 2023
Peer-review started: February 27, 2023
First decision: March 14, 2023
Revised: March 27, 2023
Accepted: May 8, 2023
Article in press: May 8, 2023
Published online: July 15, 2023
Abstract
BACKGROUND

The carcinogenesis of stomach adenocarcinoma (STAD) involves many different molecules and multiple pathways, including the NOTCH signaling pathway. As a key factor that functions as a critical link in the NOTCH pathway, mind bomb 1 (MIB1) is upregulated in various tumors and has been reported to promote cell metastasis and invasion. However, studies on the role of MIB1 in STAD are limited. Here, we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.

AIM

To elucidate the relationship between MIB1 gene and gastric cancer (GC) and provide a new idea for the treatment of GC.

METHODS

We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and disease-free survival rate using the Kaplan-Meier method. The Cancer Genome Atlas (TCGA) database provided transcript levels for MIB1 in STADs and normal tissues. As a method of distinguishing the STAD tissues from adjacent normal tissues, a receiver operating characteristic (ROC) curve was generated. Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival. Based on the LinkedOmics database, we were able to identify the coexpressed genes of the MIB1 gene, the top 50 positively correlated genes, and the top 50 negatively correlated genes. STRING was used to construct protein-protein interaction networks related to the MIB1 gene. An analysis of functional enrichment was carried out using the R package “Cluster Profiler”. The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource (TIMER) and the “GSVA package” in R.

RESULTS

According to the cBioPortal database, the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%. Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group (P = 0.0156). There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues. A high T stage was associated with increased MIB1 mRNA expression. The ROC curve analysis revealed 59.4% sensitivity and 85.6% specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248. Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels (26.4 mo vs 56.2 mo, P = 0.0330). A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.

CONCLUSION

Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma. MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.

Keywords: Stomach adenocarcinoma, Mind bomb 1, Mutation, Prognosis, Biomarker, Immune infiltration

Core Tip: NOTCH signaling pathway is involved in the occurrence and development of many tumors. Mind bomb 1 (MIB1) is one of many E3 ubiquitin ligases in ubiquitin proteasome system, which plays a key role in NOTCH signaling pathway. Several studies showed that MIB1 participated in the proliferation and metastasis of certain tumor cells, but its role in gastric cancer (GC) remained still unclear. The purpose of our study was to elucidate the relationship between MIB1 gene and GC and provide a new idea for the treatment of GC.