Screening and Identification of Biomarkers in Ascites Related to Intrinsic Chemoresistance of Serous Epithelial Ovarian Cancers |
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| Authors: | He Huang Yujie Li Jihong Liu Minghui Zheng Yanling Feng Kunhua Hu Yongwen Huang Qidan Huang |
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| Affiliation: | 1. Department of Gynecology Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.; 2. Department of Clinical Laboratory, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, P. R. China.; 3. Proteomics Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P. R. China.; University of Texas Health Science Center at San Antonio, United States of America, |
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| Abstract: | ObjectiveThe ability to predict responses to chemotherapy for serous epithelial ovarian cancer (EOC) would be valuable since intrinsically chemoresistant EOC patients (persistent or recurrent disease within 6 months) gain little benefit from standard chemotherapy. The aim of this study was to screen and identify distinctive biomarkers in ascites of serous EOC associated with intrinsic chemoresistance.MethodsProtein samples from ascites of 12 chemosensitive and 7 intrinsically chemoresistant serous EOC patients were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Furthermore, the identified proteins were validated by ELISA in ascites samples from 19 chemosensitive and 9 intrinsically chemoresistant EOC patients.ResultsThe number of spots detected in all 2-D DIGE gels ranged from 1523–1711 using DeCyder software analysis. Thirty-four spots were differentially expressed based on the criteria of an average ratio of more than 1.5 and a student t-test P value <0.05. After MALDI-TOF/TOF MS analysis, 11 differentially expressed proteins, including 3 up-regulated and 8 down-regulated proteins, in ascites of chemoresistant tumors were successfully identified. Of the four selected proteins (ceruloplasmin, apoliprotein A-IV, transthyretin and haptoglobin) in ascites tested by ELISA, only ceruloplasmin was present at significantly different levels between the chemoresistant and chemosensitive ascites samples with average concentrations of 192.2 µg/ml and 157.5 µg/ml, respectively (P = 0.001).ConclusionThe significantly up-regulated level of ceruloplasmin in the ascites fluid of intrinsic chemoresistant serous EOC patients suggests its potential as a prognostic biomarker for responses to chemotherapy. This finding prompts further investigation with a larger study in order to validate the clinical utility of ceruloplasmin. |
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