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Serum soluble Fas levels and prediction of response to platinum‐based chemotherapy in epithelial ovarian cancer
Author(s) -
Chaudhry Parvesh,
Srinivasan Radhika,
Patel Firuza D,
Gopalan Sarala,
Majumdar Siddhartha
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23213
Subject(s) - chemotherapy , medicine , fas ligand , oncology , proportional hazards model , apoptosis , biomarker , receiver operating characteristic , ovarian cancer , cancer , stage (stratigraphy) , gastroenterology , biology , programmed cell death , paleontology , biochemistry
Epithelial ovarian cancer (EOC) is treated mainly by platinum‐based combination chemotherapy. Chemotherapy induces apoptosis in which the Fas/Fas ligand pathway is important. Serum soluble Fas (sFas) is a biomarker of this pathway and functionally inhibits Fas‐/FasL‐mediated apoptosis. In this study, we have investigated the role of sFas in prediction of response to chemotherapy in EOC. Thirty‐five patients were recruited and their serum sFas levels were estimated by ELISA at 4 time points—preoperative (sFas1), postoperative (sFas2), midchemotherapy (sFas3) and at the end of chemotherapy (sFas4). The response to chemotherapy was documented clinically, radiologically and by CA‐125 levels, based on which, 2 groups were identified: primary chemosensitive ( n = 24) and primary chemoresistant ( n = 11). Based on the disease status at last follow‐up, 2 groups were identified: No Evidence of Disease ( n = 15) and Evidence of Disease ( n = 20). The primary chemoresistant tumors showed significantly higher median sFas2 levels ( p = 0.033) with the sFas2/sFas1 ratio ≥1 ( p = 0.001). A multivariate Cox proportional hazards regression model identified sFas2/sFas1 ratio as a significant factor for the prediction of response to platinum‐based chemotherapy ( p = 0.011). Receiver operating characteristic (ROC) analysis showed that at a ratio of 1.2, sFas2/sFas1 achieved a sensitivity of 82% and specificity of 100% for prediction of chemotherapeutic response. sFas2/sFas1 and sFas3/sFas1 ratio was also higher in patients with evidence of disease ( p = 0.018 and p = 0.028, respectively). Progression‐free survival rates in patients with sFas2/sFas1 ratio <1 exceeded those with ratio ≥1 ( p = 0.004). In conclusion, serum sFas is a useful biomarker for predicting response to platinum‐based chemotherapy in EOC. © 2007 Wiley‐Liss, Inc.