Zhou JW, Zhang YB, Huang ZY, Yuan YP, Jin J. Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis. World J Gastrointest Oncol 2024; 16(5): 1947-1964 [PMID: 38764850 DOI: 10.4251/wjgo.v16.i5.1947]
Corresponding Author of This Article
Jie Jin, MM, Doctor, Department of Gastroenterology, Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University, No. 252 Baili East Road, Lucheng District, Wenzhou 325000, Zhejiang Province, China. wzxyjj1999@126.com
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. May 15, 2024; 16(5): 1947-1964 Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.1947
Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis
Jian-Wei Zhou, Yi-Bing Zhang, Zhi-Yang Huang, Yu-Ping Yuan, Jie Jin
Jian-Wei Zhou, Yi-Bing Zhang, Zhi-Yang Huang, Yu-Ping Yuan, Jie Jin, Department of Gastroenterology, Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University, Wenzhou 325000, Zhejiang Province, China
Author contributions: Zhou JW conceived and designed the experiments; Zhou JW, Zhang YB, Huang ZY, Yuan YP, and Jin J carried out the experiments; Zhou JW and Jin J analyzed the data; Zhou JW and Jin J drafted the manuscript; All authors agreed to be accountable for all aspects of the work; All authors have read and approved the final manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University (No. 202401302247000596077).
Informed consent statement: Patients who participated in this research had signed informed consents.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
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: Jie Jin, MM, Doctor, Department of Gastroenterology, Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University, No. 252 Baili East Road, Lucheng District, Wenzhou 325000, Zhejiang Province, China. wzxyjj1999@126.com
Received: December 13, 2023 Peer-review started: December 13, 2023 First decision: December 19, 2023 Revised: January 4, 2024 Accepted: March 14, 2024 Article in press: March 14, 2024 Published online: May 15, 2024 Processing time: 148 Days and 12.1 Hours
Abstract
BACKGROUND
Gastric cancer (GC) has a high mortality rate worldwide. Despite significant progress in GC diagnosis and treatment, the prognosis for affected patients still remains unfavorable.
AIM
To identify important candidate genes related to the development of GC and identify potential pathogenic mechanisms through comprehensive bioinformatics analysis.
METHODS
The Gene Expression Omnibus database was used to obtain the GSE183136 dataset, which includes a total of 135 GC samples. The limma package in R software was employed to identify differentially expressed genes (DEGs). Thereafter, enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the gene modules using the clusterProfile package in R software. The protein-protein interaction (PPI) networks of target genes were constructed using STRING and visualized by Cytoscape software. The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram. The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase (GPT) in GC and normal immortalized cell lines. In addition, cell viability, cell cycle distribution, migration and invasion were evaluated by cell counting kit-8, flow cytometry and transwell assays. Furthermore, we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020. The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.
RESULTS
We selected 19214 genes from the GSE183136 dataset, among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value < 0.05. In addition, GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction, whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion, vascular smooth muscle contraction and biosynthesis of the different cofactors. Furthermore, PPI networks were constructed based on the various upregulated and downregulated genes, and there were a total 15 upregulated and 10 downregulated hub genes. After a comprehensive analysis, several hub genes, including runt-related transcription factor 2 (RUNX2), salmonella pathogenicity island 1 (SPI1), lysyl oxidase (LOX), fibrillin 1 (FBN1) and GPT, displayed prognostic values. Interestingly, it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells. Furthermore, the expression level of GPT was found to be associated with age, lymph node metastasis, pathological staging and distant metastasis (P < 0.05).
CONCLUSION
RUNX2, SPI1, LOX, FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis. GPT was significantly associated with the prognosis of GC, and its upregulation can effectively inhibit the proliferative, migrative and invasive capabilities of GC cells.
Core Tip: Five hub genes, including RUNX2, SPI1, LOX, FBN1 and GPT, were found to display prognostic values. The oncogenic role of all of these hub genes, except GPT, have been previously reported in gastric cancer. Glutamic-pyruvic transaminase (GPT) expression was significantly associated with age, lymph node metastasis, pathological staging and distant metastasis in patients with gastric cancer. Additionally, GPT was downregulated in gastric cancer cells, and its overexpression inhibited the proliferative, migrative and invasive capabilities of gastric cancer cells. Consequently, we have identified five hub genes (RUNX2, SPI1, LOX, FBN1 and GPT) as potential biomarkers and therapeutic targets for gastric diagnosis and treatment.
