Derivation and Validation of the Potential Core Genes in Pancreatic Cancer for Tumor-Stroma Crosstalk

Abstract

Background. Pancreatic cancer is a fatal malignancy with a poor prognosis. The interactions between tumor cells and stromal cells contribute to cancer progression. Pancreatic stellate cells (PSCs) play a key role in tumor-stroma crosstalk of pancreatic cancer. The in-depth exploration for tumor-stroma crosstalk is helpful to develop novel therapeutic strategies. Our aim was to identify the potential core genes and pathways in tumor-stroma crosstalk.Methods. 3 microarray datasets were from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened through bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network were used to obtain the biological roles of DEGs. The top 15 DEGs were explored by principal component analysis. We validated the top 15 DEGs expression in the tumor-stroma crosstalk model in which PSCs were treated with the mixture of Aspc-1 and Panc-1 supernatant.Results. A total of 221 genes were filtered as DEGs for tumor-stroma crosstalk. The results of principal component analysis for the top 15 DEGs can distinguish three groups. According to the KEGG enrichment, there were 8, 7, and 7 DEGs enriched in cancer related pathway, PI3K-Akt signaling pathway, and microRNAs, respectively. In the tumor-stroma crosstalk model, significant differences can be validated in the AKAP12, CLDN1, CP, FKBP1A, LAMB3, LSM4, MTMR3, PRKARIA, YWHAZ, and JUND expressions.Conclusions. These results identified the potential core genes and pathways in pancreatic cancer for tumor-stroma crosstalk, which could provide potential targets for the treatment of pancreatic cancer.