Extracellular Region Alterations in Gastric Cancer: Insights from RNA-seq Analysis and Biomarker Discovery

Gastric cancer (GC) remains a significant global health challenge, with limited effective diagnostic biomarkers and therapeutic targets. This study employs RNA sequencing (RNA-seq) analysis to investigate the transcriptomic landscape of gastric cancer (GC) in samples from three datasets: GSE۲۴۸۶۱۲, GSE۱۷۲۰۳۲, and GSE۱۶۷۵۱۲. Utilizing a conventional RNA-seq analysis pipeline along with R packages, we identified differentially expressed genes (DEGs) that are predominantly upregulated in GC tissues compared to normal tissues. Then, we employed the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to analyze these genes further, aiming to uncover potential biomarkers for gastric cancer. DAVID's functional annotation tools enabled us to categorize the DEGs based on biological processes and molecular functions, revealing pathways significantly associated with gastric cancer progression. A total of ۳۰۴ genes were found in the extracellular region, while ۶۰ genes were associated with the extracellular matrix (ECM). Venn diagram analysis revealed two common genes (MMP۱ and PKDCC) in the extracellular region across the datasets, with MMP۱ being the sole common gene in the ECM analysis. To enhance our understanding of the clinical relevance of these identified genes, we conducted gene expression and overall survival analyses using UALCAN and GEPIA. These platforms provided insights into the expression levels of the DEGs across various GC cohorts and their correlation with patient survival outcomes. Expression analysis of MMP۱ using The Cancer Genome Atlas (TCGA) data confirmed its overexpression in tumor samples compared to normal tissues, with an increasing trend observed across different tumor stages. Furthermore, overall survival (OS) analysis indicated a significant decline in OS associated with MMP۱ overexpression, underscoring its potential role as a prognostic biomarker in gastric cancer. Finally, we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify critical signaling pathways that may be implicated in gastric tumorigenesis. Notably, our findings highlighted a significant correlation between MMP۱ and the PPAR signaling pathway. Our results suggest that MMP۱ is not only a promising biomarker for GC but also a potential therapeutic target. This study underscores the utility of RNA-seq coupled with bioinformatics analyses in identifying key players in GC biology and highlights the importance of MMP۱ in disease prognosis and therapy development. Overall, these findings contribute to a deeper understanding of GC pathology and pave the way for future research aimed at improving diagnostic and therapeutic strategies.

کلیدواژه ها:

Gastric cancer ، RNA-seq ، biomarker discovery ، extracellular matrix