High Expression of RIPK2 is Associated with Taxol Resistance in Serous Ovarian Cancer

Abstract

BackgroundTaxol resistance of serous ovarian cancer is responsible for its poor prognosis, yet the underlying mechanism was still poorly understood. Thus, we probed the mechanism of taxol resistance in serous ovarian cancer with multiple bioinformatic methods to provide novel insights for potential therapy. MethodsThe differentially expressed genes (DEGs) and their relationship with overall survival (OS) and progress-free interval (PFI) of ovarian cancer patients were analyzed using gene expression datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The role of receptor interacting serine/threonine kinase 2 (RIPK2) was validated by identifying its co-expressed genes, making function analysis and generating protein-protein network (PPI). Single-sample GSEA (ssGSEA) method was used to explore the immune infiltration and genomic alterations of RIPK2 was also analyzed via cBio Cancer Genomics Portal (cBioProtal).ResultsRIPK2 was highly expressed in taxol resistant ovarian cancer cell lines, while its high expression was also linked with OS and PFI in serous ovarian cancer patients. The PPI network analysis and pathway analysis demonstrated that RIPK2 might take part in positive regulation of NF-κB transcription factor activity. Different expression level of RIPK2 was related to tumor microenvironment alteration, which might participate in formation of taxol resistance.ConclusionsOur studies suggested that high expression of RIPK2 was related to taxol resistance in serous ovarian cancer, while RIPK2 induced taxol resistance through NOD1/RIPK2/NF-κB inflammatory pathway activation and tumor microenvironment changes.