PARProceedings of Anticancer Research2208-35452208-3553Bio-Byword Scientific Publishing Pty. Ltd.10.26689/par.v9i5.12155ArticleExploring Gastric Cancer-Related Genes and Clinical Significance Analysis Based on Bioinformaticshttps://artdesignp.com/journal/PAR/9/5/10.26689/par.v9i5.12155YeLiansi,ZouChuanxin2025952025-10-13Objective: Employing bioinformatics methodologies to identify core genes intricately associated with the pathogenesis and progression of gastric cancer, and to evaluate their clinical significance. Method: Gene expression datasets GSE19826 and GSE13911 were acquired from the Gene Expression Omnibus (GEO). Differential gene expression analysis was conducted using GEO2R. Common differentially expressed genes (DEGs) were discerned via Venn diagram analysis on a bioinformatics platform. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were performed on these overlapping DEGs. A protein-protein interaction (PPI) network was constructed with the STRING database, and central hub genes were identified using Cytoscape software. The expression profiles, prognostic value, and immune infiltration correlations of these key genes were further examined utilizing the GEPIA, Kaplan-Meier plotter, Human Protein Atlas (HPA), and TIMER databases. Results: Analysis revealed 120 commonly differentially expressed genes. These genes were significantly enriched in biological pathways concerning muscle cell cytoskeleton regulation, nutrient absorption, and extracellular matrix receptor interactions. PPI network analysis highlighted 10 core genes, including COL1A1, COL1A2, BGN, THBS2, COL5A2, and TIMP1. These genes exhibited marked upregulation in GC tissues. Statistical evaluation confirmed a significant link between their elevated expression and unfavorable patient outcomes (P < 0.01). Furthermore, immune infiltration assessment indicated a positive correlation between the expression of these genes and macrophage infiltration within the tumor microenvironment, implying their involvement in modulating the immune response in GC, which could affect tumor behavior and clinical progression. Conclusion: The six genes identified may function as diagnostic biomarkers and represent promising therapeutic targets for gastric cancer.

Smyth E, Nilsson M, Grabsch H, et al., 2020, Gastric Cancer. Lancet, 396(10251): 635–648.

Conti C, Agnesi S, Scaravaglio M, et al., 2023, Early Gastric Cancer: Update on Prevention, Diagnosis and Treatment. Int J Environ Res Public Health, 20(3): 2149.

Xu B, Shi Y, Yuan C, et al., 2024, Integrated Gene-Metabolite Association Network Analysis Reveals Key Metabolic Pathways in Gastric Adenocarcinoma. Heliyon, 10(17): e37156.

Karamanos N, Piperigkou Z, Passi A, et al., 2021, Extracellular Matrix-Based Cancer Targeting. Trends Mol Med, 27(10): 1000–1013.

Wieboldt R, Laubli H, 2022, Glycosaminoglycans in Cancer Therapy. Am J Physiol Cell Physiol, 322(6): C1187–C1200.

Wei J, Hu M, Huang K, et al., 2020, Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression. Int J Mol Sci, 21(17): 5983.

Chen S, Li Y, Zhu Y, et al., 2022, SERPINE1 Overexpression Promotes Malignant Progression and Poor Prognosis of Gastric Cancer. J Oncol, 2022: 2647825.

Xu X, Zhang L, Qian Y, et al., 2022, A SERPINE1-Based Immune Gene Signature Predicts Prognosis and Immunotherapy Response in Gastric Cancer. Pharmaceuticals (Basel), 15(11): 1401.

Cikach F, Koch C, Mead T, et al., 2018, Massive Aggrecan and Versican Accumulation in Thoracic Aortic Aneurysm and Dissection. JCI Insight, 3(5): e97167.

Croix B, Rago C, Velculescu V, et al., 2000, Genes Expressed in Human Tumor Endothelium. Science, 289(5482): 1197–1202.

Li J, Ding Y, Li A, 2016, Identification of COL1A1 and COL1A2 as Candidate Prognostic Factors in Gastric Cancer. World J Surg Oncol, 14(1): 297.

Li A, Si J, Shang Y, et al., 2010, Construction of COL1A1 Short Hairpin RNA Vector and Its Effect on Cell Proliferation and Migration of Gastric Cancer Cells. Journal of Zhejiang University, 39(3): 257–263.

Paluch E, Aspalter I, Sixt M, 2016, Focal Adhesion-Independent Cell Migration. Annu Rev Cell Dev Biol, 32: 469–490.

Hu M, Zhu S, Xiong S, et al., 2019, MicroRNAs and the PTEN/PI3K/Akt Pathway in Gastric Cancer. Oncol Rep, 41(3): 1439–1454.

Jin Y, Song X, Sun X, et al., 2023, Up-Regulation of Collagen Type V Alpha 2 (COL5A2) Promotes Malignant Phenotypes in Gastric Cancer Cell via Inducing Epithelial-Mesenchymal Transition (EMT). Open Med (Wars), 18(1): 20220593.

Li H, Zhong A, Li S, et al., 2017, The Integrated Pathway of TGFβ/Snail with TNFα/NFκB May Facilitate the Tumor-Stroma Interaction in the EMT Process and Colorectal Cancer Prognosis. Sci Rep, 7(1): 4915.

Schulz G, Grimm T, Sers C, et al., 2019, Prognostic Value and Association with Epithelial-Mesenchymal Transition and Molecular Subtypes of the Proteoglycan Biglycan in Advanced Bladder Cancer. Urol Oncol, 37(8): 530.e9–530.e18.

Wu H, Xiang Z, Huang G, et al., 2023, BGN/FAP/STAT3 Positive Feedback Loop Mediated Mutual Interaction Between Tumor Cells and Mesothelial Cells Contributes to Peritoneal Metastasis of Gastric Cancer. Int J Biol Sci, 19(2): 465–483.

Bornstein P, 2009, Thrombospondins Function as Regulators of Angiogenesis. J Cell Commun Signal, 3(3–4): 189–200.

Sun R, Wu J, Chen Y, et al., 2014, Down Regulation of Thrombospondin2 Predicts Poor Prognosis in Patients with Gastric Cancer. Mol Cancer, 13(1): 225.

Chang Z, Gao Y, Chen P, et al., 2024, THBS2 Promotes Gastric Cancer Progression and Stemness via the Notch Signaling Pathway. Am J Cancer Res, 14(7): 3433–3450.

Thaysen-Andersen M, Thøgersen I, Lademann U, et al., 2008, Investigating the Biomarker Potential of Glycoproteins Using Comparative Glycoprofiling—Application to Tissue Inhibitor of Metalloproteinases-1. Biochim Biophys Acta, 1784(3): 455–463.

Fuksiewicz M, Kotowicz B, Rutkowski A, et al., 2015, The Matrix Metalloproteinase-7 and Pro-Enzyme of Metalloproteinase-1 as a Potential Marker for Patients with Rectal Cancer Without Distant Metastasis. Tumour Biol, 36(5): 3629–3635.

Grunnet M, Mau-Sørensen M, Brunner N, 2013, Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) as a Biomarker in Gastric Cancer: A Review. Scand J Gastroenterol, 48(8): 899–905.