Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission afterinitial surgery and chemotherapy. However, most patients die within <5 years due to episodesof recurrences resulting from the growth of residual chemoresistant cells. In an effort to identifymechanisms associated with chemoresistance and recurrence, we compared the expression of proteinsin ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained atdiagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR)by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteinswere identified. Using a stringent selection criterion to define only significantly differentially expressedproteins, we report identification of 353 proteins. There were significant differences in proteinsencoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-celladhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/argininesynthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichmentof metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells.In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cellsfrom CN and CR ovarian cancer patients.
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