Chaudhry Parvesh, Srinivasan Radhika, Patel Firuza D, Gopalan Sarala, Majumdar Siddhartha
Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Int J Cancer. 2008 Apr 15;122(8):1716-21. doi: 10.1002/ijc.23213.
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.
上皮性卵巢癌（EOC）主要通过铂类联合化疗进行治疗。化疗诱导细胞凋亡，其中Fas/Fas配体途径很重要。血清可溶性Fas（sFas）是该途径的生物标志物，在功能上可抑制Fas-/FasL介导的细胞凋亡。在本研究中，我们调查了sFas在预测EOC化疗反应中的作用。招募了35名患者，并在4个时间点通过酶联免疫吸附测定（ELISA）评估其血清sFas水平，即术前（sFas1）、术后（sFas2）、化疗中期（sFas3）和化疗结束时（sFas4）。根据临床、影像学和CA-125水平记录化疗反应，据此将患者分为两组：原发性化疗敏感组（n = 24）和原发性化疗耐药组（n = 11）。根据最后一次随访时的疾病状态，将患者分为两组：无疾病证据组（n = 15）和有疾病证据组（n = 20）。原发性化疗耐药肿瘤的sFas2水平中位数显著更高（p = 0.033），sFas2/sFas1比值≥1（p = 0.001）。多变量Cox比例风险回归模型确定sFas2/sFas1比值是预测铂类化疗反应的重要因素（p = 0.011）。受试者工作特征（ROC）分析表明，当比值为1.2时，sFas2/sFas1预测化疗反应的灵敏度为82%，特异性为100%。有疾病证据的患者中，sFas2/sFas1和sFas3/sFas1比值也更高（分别为p = 0.018和p = 0.028）。sFas2/sFas1比值<1的患者无进展生存率超过比值≥者（p = 0.004）。总之，血清sFas是预测EOC铂类化疗反应的有用生物标志物。
