Biomarkers in the ascites, cytoskeletal protein (ACTB) was excluded from this analysis.The ELISA results confirmed our MALDI-TOF/TOF MS findings in that the level of ceruloplasmin was significantly higher in chemoresistant than in chemosensitive ascites. The average concentration of ceruloplasmin was 157.5 mg/ml in the chemosensitive group and 192.2 mg/ml in the chemoresistant group (P = 0.001), while the levels of Apo-AIV, transthyretin and haptoglobin were not significantly different between the two groups. These results are summarized in Table 3.DiscussionThe prognosis of ovarian cancer is known to be strongly associated with the length of the platinum-free interval from the primary first-line platinum-based combination chemotherapy treatment to relapse. The longer this interval lasts, the better the response rate to subsequent chemotherapy [8]. Thus, standardBiomarkers for Chemoresistant Ovarian CancerFigure 1. Comparison of survival between chemosensitive and intrinsic chemoresistant serous EOC patients. A significant difference (P = 0.007) was observed in survival, which favored patients with chemosensitive tumors. doi:10.1371/journal.pone.0051256.gchemotherapy is largely non-beneficial for intrinsically chemoresistant ovarian cancer patients (with persistent or recurrent disease CUDC-427 within 6 months). The ability to predict the response to standard chemotherapy in these patients would be extremely valuable in allowing the early use of individualized therapeutics to help prolong survival and avoid unnecessary side effects of ineffective treatments. We have noted that many advanced stage ovarian cancer patients present with rapid growth of intraperitoneal tumors along with abdominal distention as a result of accumulation of ascites fluid in the peritoneal cavity. Mechanistically, ascites formation occurs as malignant cells secrete proteins, growth factors and cytokines that cause neovascularization, angiogenesis, increased fluid filtration and/or lymphatic obstruction, resulting in the buildup of serum-like fluid within the abdomen [9,10]. The rich medium provides support for malignant cells to proliferate and further metastasize despite the lack of matrix substrata, allowing these cells to overcome the apoptosis associated with loss of attachment. This implies that malignant cells and mesothelial cells in ascites up-regulate survival signals in order to persist in the hypoxic but otherwise rich liquid milieu [11]. Thus, ascites is an excellent reservoir for the identification of useful cancer biomarkers, especially in EOC patients [12]. In a study by Kislinger’s group, ascites were separated into cellular and fluid fractions, followed by mass spectrometry analysis of each fraction [13]. While over 2,500 proteins within ascites were identified, only 229 proteins were found in the fluid fraction. After integrated computational analysis of the ascites proteome combined with proteomic data from human plasma and urine microarray data sets and protein rotein Interaction Database I2D, 80 candidate serological ovarian cancer biomarkers wereselected for further validation. Kuk and colleagues also carried out proteomic analysis of ascites fluid based on multiple separation and fractionation techniques [14]. A total of 52 proteins were selected from 445 unique proteins in the ascites fluid as good candidates for ovarian cancer biomarkers in CPI-203 future investigations. These authors all found proteomic analysis to be a significant resource for ovarian.Biomarkers in the ascites, cytoskeletal protein (ACTB) was excluded from this analysis.The ELISA results confirmed our MALDI-TOF/TOF MS findings in that the level of ceruloplasmin was significantly higher in chemoresistant than in chemosensitive ascites. The average concentration of ceruloplasmin was 157.5 mg/ml in the chemosensitive group and 192.2 mg/ml in the chemoresistant group (P = 0.001), while the levels of Apo-AIV, transthyretin and haptoglobin were not significantly different between the two groups. These results are summarized in Table 3.DiscussionThe prognosis of ovarian cancer is known to be strongly associated with the length of the platinum-free interval from the primary first-line platinum-based combination chemotherapy treatment to relapse. The longer this interval lasts, the better the response rate to subsequent chemotherapy [8]. Thus, standardBiomarkers for Chemoresistant Ovarian CancerFigure 1. Comparison of survival between chemosensitive and intrinsic chemoresistant serous EOC patients. A significant difference (P = 0.007) was observed in survival, which favored patients with chemosensitive tumors. doi:10.1371/journal.pone.0051256.gchemotherapy is largely non-beneficial for intrinsically chemoresistant ovarian cancer patients (with persistent or recurrent disease within 6 months). The ability to predict the response to standard chemotherapy in these patients would be extremely valuable in allowing the early use of individualized therapeutics to help prolong survival and avoid unnecessary side effects of ineffective treatments. We have noted that many advanced stage ovarian cancer patients present with rapid growth of intraperitoneal tumors along with abdominal distention as a result of accumulation of ascites fluid in the peritoneal cavity. Mechanistically, ascites formation occurs as malignant cells secrete proteins, growth factors and cytokines that cause neovascularization, angiogenesis, increased fluid filtration and/or lymphatic obstruction, resulting in the buildup of serum-like fluid within the abdomen [9,10]. The rich medium provides support for malignant cells to proliferate and further metastasize despite the lack of matrix substrata, allowing these cells to overcome the apoptosis associated with loss of attachment. This implies that malignant cells and mesothelial cells in ascites up-regulate survival signals in order to persist in the hypoxic but otherwise rich liquid milieu [11]. Thus, ascites is an excellent reservoir for the identification of useful cancer biomarkers, especially in EOC patients [12]. In a study by Kislinger’s group, ascites were separated into cellular and fluid fractions, followed by mass spectrometry analysis of each fraction [13]. While over 2,500 proteins within ascites were identified, only 229 proteins were found in the fluid fraction. After integrated computational analysis of the ascites proteome combined with proteomic data from human plasma and urine microarray data sets and protein rotein Interaction Database I2D, 80 candidate serological ovarian cancer biomarkers wereselected for further validation. Kuk and colleagues also carried out proteomic analysis of ascites fluid based on multiple separation and fractionation techniques [14]. A total of 52 proteins were selected from 445 unique proteins in the ascites fluid as good candidates for ovarian cancer biomarkers in future investigations. These authors all found proteomic analysis to be a significant resource for ovarian.
