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Seventypercentofovariancancerpatientsdieduetoconsecutiveepisodesofrecurrencesresultingfromthere-growth of ovarian tumor cells resistant to conventional chemotherapies. In an effort to identify chemoresistance mechanisms, we comparedtheexpressionofgenesintumorcellsisolatedfromtheascitesofadvanced-stageserousovariancancerpatientsprior to(chemonaive,CN)andafterchemotherapytreatments(chemoresistant/recurrent,CR).Anovel,recentlypublishedmethodwas used for the isolation of tumor cells from the ascites of CN and CR patients. Illumina HT-12 platform was used to assess the differentialexpressionofgenes(DEGs)betweentheisolatedtumorcellsfromtheascitesofCNandCRpatients.Theidentification ofDEGswasachievedbycomparingthegeneticsignaturesofCNversusCRsamplesbyameanexpressionratio(foldchange)of 2 and P < 0.05. Validation of selected genes was performed by quantitative Real Time Polymerase Chain Reaction (qRT-PCR). The dominant canonical pathways in the CR versus CN tumor cells were determined by Ingenuity Pathway Analysis. Gene expressionanalysisrevealeddifferentialexpressionof414genes,with179genesupregulatedand235downregulatedintheCR group. There were significant differences in gene expressions encoding for proteins involved with cancer stem cells, cell-cell adhesion, embryonic development, tumor suppression, immune surveillance, retinoic acid and energy metabolism in tumor cells isolated from CR compared to CN patients. Pathway analysis revealed that changes in cell cycle pathways, prominently those involved with mitosis and polo-like kinase (PLK1), G2/M DNA damage and proteins linked with cell cycle checkpoint regulation associated with chemoresistance. This preliminary molecular profiling, on a small number of patient samples, suggests an importantdiscriminationofgenesintheisolatedtumorcellsderivedfromtheascitesofCNandCRpatients.Thistypeofstudyon a larger cohort of samples may have important clinical implications for the development of therapeutic strategies to overcome chemoresistance and associated recurrences in ovarian cancer patients.

Distinct molecular signature of recurrent ovarian tumor cells isolated from the ascites of advanced-stage serous ovarian cancer patients