Comparative study of microarray analysis in gastrointestinal carcinomas: identification of common genes and signaling pathways

Gastrointestinal carcinomas, including esophageal, stomach, colon, colorectal, hepatocellular, bile duct, and pancreatic cancers, present significant challenges in oncology research due to their complex genetic underpinnings. Given that these malignancies share a common embryonic endodermal origin, it is anticipated that they exhibit important genetic commonalities and similar molecular pathways. Identifying these convergences, alongside unique genes, can facilitate the development of predictive biomarkers and targeted therapies. Methods: This study utilized microarray data sourced from the Gene Expression Omnibus (GEO) database. Selected datasets included tumor samples paired with healthy controls, adhering to stringent criteria for carcinoma classification. The datasets analyzed comprised esophageal (GSE۲۰۳۴۷, GSE۲۹۰۰۱), colorectal (GSE۲۰۹۱۶, GSE۲۳۸۷۸), colon (GSE۶۸۴۶۸), liver (GSE۶۰۵۰۲, GSE۱۴۵۲۰), bile duct (GSE۴۵۰۰۱, GSE۱۰۷۹۴۳), pancreatic (GSE۱۹۶۵۰, GSE۴۵۷۶۵), and gastric (GSE۲۹۹۹۸) cancers. Following data normalization, differentially expressed genes (DEGs) were identified across the cancers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to elucidate the biological functions associated with these DEGs. Protein-protein interaction (PPI) networks were constructed using String and Cytoscape, and the Maximal Clique Centrality (MCC) method identified the top ۳۰ hub genes for up-regulated and down-regulated expressions separately. Clinical relevance was further assessed using The Cancer Genome Atlas (TCGA) and DepMap resources. Results: The analysis revealed significant overlaps in DEGs across the studied cancers. For instance, the analysis showed that colon and colorectal cancers had ۲۲۷ common up-regulated genes, while colon and esophagus had ۱۴۸, and bile duct and colorectal had ۱۲۸. Conversely, down-regulated gene overlaps included ۲۷۹ between liver and bile duct, ۴۳۴ between colon and colorectal, and ۱۹۵ between colorectal and pancreas. Among the shared hub genes, several potential biomarkers were identified. Notably, up-regulated genes such as MELK, TOP۲A, and TTK, which are involved in apoptosis and cell proliferation, emerged as hubs across most gastrointestinal carcinomas. However, comprehensive commonalities among all organs were not observed for down-regulated genes, highlighting unique gene expression profiles. Certain genes such as CDCA۳ in colorectal cancer, NDC۸۰ in Hepatocellular carcinoma, and MKI۶۷ in cholangiocarcinoma were specialized targets and are suggested to be investigated in drug studies. The enrichment analysis revealed that the Cell Cycle and p۵۳ signaling pathways were significantly up-regulated, while drug metabolism-cytochrome P۴۵۰ and fatty acid degradation signaling pathways were notably down-regulated across many gastrointestinal carcinomas. Discussion: This comparative study underscores the significance of microarray analysis in unraveling the molecular basis of gastrointestinal carcinomas. Our findings contribute to ongoing efforts to identify reliable biomarkers for early diagnosis and potential drug targets for personalized therapies. Future research should focus on validating these biomarkers in clinical settings and investigating their roles in the progression of gastrointestinal cancers and responses to personalized treatments.

کلیدواژه ها:

Gastrointestinal carcinoma ، Differentially expressed genes (DEGs) ، Biomarkers ، Network analysis