Exploring COL۱A۱, COL۱A۲, FN۱, and MMP۲ as Potential Prognostic Biomarkers in Gastric Cancer

Gastric cancer ranks as the fifth most prevalent malignancy worldwide, and the lack of reliable biomarkers significantly complicates its diagnosis and treatment. By analyzing the GSE۵۴۱۲۹ dataset, we identified ۷۶۳ genes with different expression levels. KEGG pathway and GO analysis identified five hub genes, including COL۱A۱, FN۱, MMP۲, MMP۹, and COL۱A۲. These cancers originate from the glandular cells in the innermost lining of the stomach (the mucosa). The intestinal type generally presents a slightly better prognosis. The cancer cells are more likely to exhibit specific genetic alterations that may permit treatment with targeted drug therapy. The diffuse type tends to proliferate and metastasize more rapidly. It is less common than the intestinal type and is generally more difficult to treat. Nested case-control studies have shown that Helicobacter pylori infection significantly increases the risk of gastric cancer, affecting both the intestinal and diffuse subtypes. This research sought to discover novel genes linked to gastric cancer to enhance prognosis prediction and create more effective treatment approaches. Material and Method: The dataset labeled GSE۵۴۱۲۹ was obtained using the GEO query package in R, comprising ۱۱۱ cancer samples and ۲۱ normal samples. Genes that were differently expressed (DEGs) were identified based on the criteria of |log۲fc|>۲ and an adjusted p-value of less than ۰.۰۵. A network of protein-protein interactions (PPI) was created using the STRING database and analyzed with Cytoscape software. Modules and hub genes were screened using the molecular complex detection (MCODE) plugin was used with default parameters: degree (cutoff=۰.۲, hair cut=on, node score cut-off =۰.۲, k-core = ۲, and max. (depth = ۱۰۰). The first cluster, whit a score of ۲۰.۶۴۵ and including ۳۲ genes, was selected. Hub genes were identified using the MCC method through the CytoHubba plugin. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were conducted using the prognostic value of hub genes was performed through the Kaplan-Meier plotter database.(http://Kmplot.com/analysis). Result: A total of ۷۶۳ differentially expressed genes (DEGs) were identified, with ۳۵۵ up-regulated and ۴۰۸ down regulated. The KEGG pathway analysis revealed significant enrichment in the metabolism of xenobiotics by cytochrome P۴۵۰ (hsa۰۰۹۸۰) pathway. According to Gene Ontology (GO) annotation, the xenobiotic metabolic process (GO:۰۰۰۶۸۰۵), extracellular region (GO:۰۰۰۵۵۷۶), and extracellular matrix structural constituent (GO:۰۰۰۵۲۰۱) were enriched in the biological process, cellular component, and molecular function categories, respectively. Hub genes were identified using the top ۵ genes in the maximal clique centrality (MCC) algorithm from the pivotal cluster (score = ۲۰.۶۴۵), including collagen type I alpha ۱ chain (COL۱A۱), fibronectin ۱ (FN۱), matrix metallopeptidase ۲ (MMP۲), matrix metallopeptidase ۹(MMP۹), and collagen type I alpha ۲ chain (COL۱A۲). Survival analysis indicated that the overexpression of these genes, except for MMP۹, was associated with a reduced overall survival rate. Conclusion: In this research, four hub genes were identified, named, MMP۲, COL۱A۱, FN۱, and COL۱A۲ through bioinformatics analysis. These genes were significantly associated with poor prognosis in gastric cancer patients. They may serve as potential biomarkers and therapeutic targets for early diagnosis and disease prevention.

کلیدواژه ها:

Gastric cancer ، Hub genes ، Bioinformatics ، Survival analysis ، Prognosis