Identification of key genes and signaling pathways involved in metastatic peritoneal cancer originating from gastric and pancreatic cancers: A bioinformatics study

: Metastatic peritoneal cancer, which can originate from gastric and pancreatic cancers, poses an important clinical challenge due to its aggressive behavior and poor prognosis. Understanding the underlying molecular mechanisms that drive this metastatic process is crucial for developing targeted interventions. This study aims to perform a bioinformatics analysis to discover the genes and pathways involved in the metastatic spread of these cancers to the peritoneum. Methods: Three gene expression datasets were selected from the GEO database: GSE۱۷۲۱۵۹ for peritoneal metastatic samples, GSE۷۹۹۷۳ and GSE۱۵۴۷۱ for non-metastatic gastric and pancreatic cancer samples, and the corresponding healthy tissue controls. Data normalization was performed using the RMA algorithm in R programming language and differentially expressed genes (DEGs) were identified. Three main analyses were performed: ۱) comparison of peritoneal metastatic samples with non-metastatic cancer samples to identify genes involved in metastasis, ۲) comparison of peritoneal metastatic samples with healthy tissue controls, and ۳) comparison of non-metastatic samples with healthy tissue controls. Protein-protein interaction (PPI) networks were constructed and hub genes were identified using the STRING database and Cytoscape software with the MCC algorithm. Pathway enrichment analyses were performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to characterize the underlying biological processes and signaling pathways. The GEPIA database was used for gene expression validation and survival analysis. Results: The analysis of peritoneal metastatic samples showed ۸۳۹ and ۱۱۳۶ DEGs for gastric and pancreatic cancers, respectively, compared to their non-metastatic counterparts. Of these, ۳۶۰ genes were common in both types of cancer, indicating their potential role in peritoneal metastasis. CCL۵, CCR۵, and FCGR۳B genes for the stomach and CCNB۱, CDK۱, and DLGAP۵ genes for the pancreas are the superior hub genes that are likely to cause metastasis of non-metastatic gastric and pancreas cancers. In the comparative analysis of the pathways involved in the metastasis of both organs, common pathways were found, among the most important of these pathways, we can mention Phagosome and Cell adhesion molecules. Discussion: This comprehensive bioinformatics study provides valuable insights into common and unique molecular signatures of peritoneal metastasis in gastric and pancreatic cancers. Identifying common hub genes and pathways in organs involved in this metastatic process can help to develop targeted therapeutic strategies such as drug design and prognostic biomarkers. Further functional validation and clinical studies of these findings will help improve the management of metastatic peritoneal cancer.

کلیدواژه ها:

Peritoneal metastasis ، Gastric cancer ، Pancreatic cancer ، Differentially expressed genes (DEG) ، Network analysis