Transcriptomic profiles of ovarian cancer cells incubated with autologous ascitic fluids from patients before and after chemotherapy
Ovarian cancer is characterized by transcoelomic metastasis into the peritoneal cavity. The peritoneal malignant ascites is enriched with ovarian cancer cells and a small amount of tumor-associated immune cells which create a unique microenvironment actively contributing to progression of the disease. However, it is remain unclear how chemonaive and post-chemotherapy ovarian cancer ascitic fluids influence on cancer cells. To address this issue, we performed RNAseq analysis of primary cultures of ovarian cancer cells incubated for 3 days in the presence of ascites from the same patients before and after chemotherapy. We found that ascites after therapy causes a significant changes in transcriptomic profiles of cancer cells, and these changes are similar in samples obtained from all patients (n=4). Enrichment analysis of differentially expressed genes in tumor cells incubated with ascites after chemotherapy identified prominent up-regulation of genes associated with DNA repair, mitotic cell cycle regulation, and cell cycle checkpoints. These findings demonstrate how ascitic fluids persisted after chemotherapy can contribute to the emergence of tumor chemoresistance during short time period. Overall design: We established primary cultures of ovarian cancer cells isolated from ascitic fluids of 4 ovarian cancer patients before chemotherapy. Early passages of these cancer cells were incubated for 3 days in the presence of autologous ascitic fluids (25% v/v) from patients before and after chemotherapy. Total RNA was isolated from early passages of cancer cells. Transcriptome profiles for the obtained samples were generated using HiSeq 2500 and NextSeq 500 System (Illumina).