Early Diagnostic and Prognostic Biomarkers for Gastric Cancer: Systems-level Molecular Basis of Subsequent Alterations in Gastric Mucosa from Chronic Atrophic Gastritis to Gastric Cancer

Overview

Journal J Genet Eng Biotechnol

Specialty Biotechnology

Date 2023 Aug 18

PMID 37594635

Authors

Tamizh G Selvan

Pavan Gollapalli

Santosh H S Kumar

Sudeep D Ghate

Affiliations

Soon will be listed here.

Abstract

Purpose: It is important to comprehend how the molecular mechanisms shift when gastric cancer in its early stages (GC). We employed integrative bioinformatics approaches to locate various biological signalling pathways and molecular fingerprints to comprehend the pathophysiology of the GC. To facilitate the discovery of their possible biomarkers, a rapid diagnostic may be made, which leads to an improved diagnosis and improves the patient's prognosis.

Methods: Through protein-protein interaction networks, functional differentially expressed genes (DEGs), and pathway enrichment studies, we examined the gene expression profiles of individuals with chronic atrophic gastritis and GC.

Results: A total of 17 DEGs comprising 8 upregulated and 9 down-regulated genes were identified from the microarray dataset from biopsies with chronic atrophic gastritis and GC. These DEGs were primarily enriched for CDK regulation of DNA replication and mitotic M-M/G1 phase pathways, according to KEGG analysis (p > 0.05). We discovered two hub genes, MCM7 and CDC6, in the protein-protein interaction network we obtained for the 17 DEGs (expanded with increased maximum interaction with 110 nodes and 2103 edges). MCM7 was discovered to be up-regulated in GC tissues following confirmation using the GEPIA and Human Protein Atlas databases.

Conclusion: The elevated expression of MCM7 in both chronic atrophic gastritis and GC, as shown by our comprehensive investigation, suggests that this protein may serve as a promising biomarker for the early detection of GC.

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References

Clarke D, Kuleshov M, Schilder B, Torre D, Duffy M, Keenan A . eXpression2Kinases (X2K) Web: linking expression signatures to upstream cell signaling networks. Nucleic Acids Res. 2018; 46(W1):W171-W179. PMC: 6030863. DOI: 10.1093/nar/gky458. View

Kong D, Yao F . CDC6 is a possible biomarker for hepatocellular carcinoma. Int J Clin Exp Pathol. 2021; 14(7):811-818. PMC: 8339721. View

Hanna E, Zaki N, Amin A . Detecting Protein Complexes in Protein Interaction Networks Modeled as Gene Expression Biclusters. PLoS One. 2015; 10(12):e0144163. PMC: 4671556. DOI: 10.1371/journal.pone.0144163. View

Xie Y, Mu C, Kazybay B, Sun Q, Kutzhanova A, Nazarbek G . Network pharmacology and experimental investigation of extract targeted kinase with herbzyme activity for potent drug delivery. Drug Deliv. 2021; 28(1):2187-2197. PMC: 8526013. DOI: 10.1080/10717544.2021.1977422. View

Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K . KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2016; 45(D1):D353-D361. PMC: 5210567. DOI: 10.1093/nar/gkw1092. View

Arici D, Tuncer E, Ozer H, Simek G, Koyuncu A . Expression of retinoblastoma and cyclin D1 in gastric carcinoma. Neoplasma. 2009; 56(1):63-7. DOI: 10.4149/neo_2009_01_63. View

Ge S, Jung D, Yao R . ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics. 2019; 36(8):2628-2629. PMC: 7178415. DOI: 10.1093/bioinformatics/btz931. View

Hamashima C . Current issues and future perspectives of gastric cancer screening. World J Gastroenterol. 2014; 20(38):13767-74. PMC: 4194560. DOI: 10.3748/wjg.v20.i38.13767. View

Raman K . Construction and analysis of protein-protein interaction networks. Autom Exp. 2010; 2(1):2. PMC: 2834675. DOI: 10.1186/1759-4499-2-2. View

10.

Nelson D, Al Hrout A, Alzahmi A, Chaiboonchoe A, Amin A, Salehi-Ashtiani K . Molecular Mechanisms behind Safranal's Toxicity to HepG2 Cells from Dual Omics. Antioxidants (Basel). 2022; 11(6). PMC: 9219844. DOI: 10.3390/antiox11061125. View

11.

Szklarczyk D, Morris J, Cook H, Kuhn M, Wyder S, Simonovic M . The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2016; 45(D1):D362-D368. PMC: 5210637. DOI: 10.1093/nar/gkw937. View

12.

Huang T, Huo L, Wang Y, Xia W, Wei Y, Chang S . Epidermal growth factor receptor potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers. Cancer Cell. 2013; 23(6):796-810. PMC: 3703149. DOI: 10.1016/j.ccr.2013.04.027. View

13.

Lambert S, Jolma A, Campitelli L, Das P, Yin Y, Albu M . The Human Transcription Factors. Cell. 2018; 172(4):650-665. DOI: 10.1016/j.cell.2018.01.029. View

14.

Yang J, Li D, Zhang Y, Guan B, Gao P, Zhou X . The Expression of MCM7 is a Useful Biomarker in the Early Diagnostic of Gastric Cancer. Pathol Oncol Res. 2017; 24(2):367-372. DOI: 10.1007/s12253-017-0251-1. View

15.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

16.

Hu C, Ma Z, Zhu J, Fan Y, Tuo B, Li T . Physiological and pathophysiological roles of acidic mammalian chitinase (CHIA) in multiple organs. Biomed Pharmacother. 2021; 138:111465. DOI: 10.1016/j.biopha.2021.111465. View

17.

Liu X, Wang S, Li J, Zhang J, Liu D . Regulatory effect of traditional Chinese medicines on signaling pathways of process from chronic atrophic gastritis to gastric cancer. Chin Herb Med. 2022; 14(1):5-19. PMC: 9476726. DOI: 10.1016/j.chmed.2021.10.008. View

18.

Lu H, Zhou Q, He J, Jiang Z, Peng C, Tong R . Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials. Signal Transduct Target Ther. 2020; 5(1):213. PMC: 7511340. DOI: 10.1038/s41392-020-00315-3. View

19.

Pathan M, Keerthikumar S, Ang C, Gangoda L, Quek C, Williamson N . FunRich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics. 2015; 15(15):2597-601. DOI: 10.1002/pmic.201400515. View

20.

Qiu Y, Wang W, Zhang B, Mei L, Shi Z . MCM7 amplification and overexpression promote cell proliferation, colony formation and migration in esophageal squamous cell carcinoma by activating the AKT1/mTOR signaling pathway. Oncol Rep. 2017; 37(6):3590-3596. DOI: 10.3892/or.2017.5614. View