Identification of key pathways and genes changes in pancreatic cancer cells (BXPC-3) after cross-talk with primary pancreatic stellate cells using bioinformatics analysis

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with poor prognosis, and the interaction between activated pancreatic stellate cells (PSCs) and PDAC cells plays an important role in the development of PDAC. The aim of this study was to identify gene changes in BXPC-3 after cross-talk with PSCs and reveal their potential mechanisms. The gene expression profiling analysis of BXPC-3 was completed after co-culture with primary PSCs for 48 h. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and the differentially expressed genes (DEGs) were identified by Agilent GeneSpring GX software. In total, 3657 DEGs were identified in BXPC-3, including 1881 up-regulated genes and 1776 downregulated genes. GO analysis results showed that upregulated DEGs were significantly enriched in biological processes (BP), including peptide metabolic process, response to stress and electron transport chain; the downregulated DEGs were significantly enriched in biological processes, including signaling, multicellular organism development and anatomical structure development. KEGG pathway analysis revealed that 19 pathways were upregulated and 32 pathways were downregulated, and that upregulated DEGs were enriched in protein export and glutathione metabolism, while the downregulated DEGs were enriched in axon guidance and focal adhesion. The top 10 upregulated genes and the top 10 downregulated genes were identified. By constructing PPI network, we selected out 10 key genes (TP53, SRC, IL6, JUN, ISG15, CAD, STAT1, OAS3, OAS1, VIM) and significant pathways. The associated survival analysis was performed and the SRC, IL-6, ISG15, STAT1, OAS3, OAS1 and VIM were proved to be related to worse overall survival time of PDAC patients. In conclusion, the present study indicated that the identified DEGs promote our understanding of the molecular mechanisms underlying the interaction between pancreatic cancer cells and PSCs and might be used as molecular targets in the future to study the role of tumor microenvironment in the progression of PDAC.

Biological Characterization and Clinical Value of OAS Gene Family in Pancreatic Cancer

“…This study may assist clinicians to choose targets for immunotherapy and make personalized treatment strategy for pancreatic cancer. Tang et al (63) reported that OAS1 and OAS3 are key gene changes in pancreatic cancer cells (BXPC-3) compared with primary pancreatic stellate cells using bioinformatics analysis. Glaß et al (64) showed that OASL is a driver and therapeutic target candidate in pancreatic ductal adenocarcinoma.…”

Construction of an RNA-Binding Protein-Related Prognostic Model for Pancreatic Adenocarcinoma Based on TCGA and GTEx Databases

“…A study from Robert et al indicated that OAS1 expression was correlated with azacytidine (AZA) sensitivity in the NCI-60 tumor cell lines and was a biomarker for predicting AZA sensitivity of tumor cells (Banerjee et al, 2019). Besides, one gene expression profiling combining bioinformatics analysis in regard to PAAD identified that OAS1 was related to worse prognosis of PAAD (Tang et al, 2019). A basic experiment showed that pancreatic cancer cell lines with high OAS expression were resistant to oncolytic virus therapy (Moerdyk-Schauwecker et al, 2013).…”

Comprehensive analysis of prognostic immune‑related genes associated with the tumor microenvironment of pancreatic ductal adenocarcinoma

“…There are three types of OAS proteins in humans, OAS1, OAS2 and OAS3. OAS1 has been demonstrated to be associated with pancreatic cancer and prostate cancer ( 41 , 45 ). Oncolytic virus therapy is a promising treatment option for pancreatic cancer; however, high expression levels of OAS in cell lines are associated with resistance to this therapy ( 46 ).…”

“…The discovery of the following four genes provides guidance for searching for targeted genes for immunotherapy of pancreatic cancer. It has been reported that immune response by four IRGs (OAS1, MET, IL1R2 and IL20RB) is associated with the prognosis of pancreatic cancer (39)(40)(41)(42). The OAS system is an antiviral signaling pathway induced by interferon and OAS genes that are described as interferon-stimulated genes (43,44).…”