Serum soluble Fas levels and prediction of response to platinum-based chemotherapy in epithelial ovarian cancer.
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 > or =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 > or =1 (p = 0.004). In conclusion, serum sFas is a useful biomarker for predicting response to platinum-based chemotherapy in EOC.
Chaudhry
Parvesh
P
Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Srinivasan
Radhika
R
Patel
Firuza D
FD
Gopalan
Sarala
S
Majumdar
Siddhartha
S
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D002277:Carcinoma / Q000097:blood* / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000601:surgery; D017671:Platinum Compounds / Q000008:administration & dosage; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D019014:fas Receptor / Q000097:blood*
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D017671:Platinum Compounds; D019014:fas Receptor