Konno R, Takano T, Sato S, Yajima A
Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan.
Clin Cancer Res. 2000 Sep;6(9):3576-80.
The Fas-Fas ligand system is important in apoptosis mediated by CTLs and natural killer cells. The suppression of apoptosis contributes to carcinogenesis, as well as to a resistance to chemotherapy and radiotherapy. Circulating soluble Fas (sFas), which is generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We investigated sFas levels in 64 patients with gynecological malignancies (28 cervical carcinomas, 18 endometrial carcinomas, and 18 ovarian carcinomas) and in 24 healthy female donors by using a Fas-specific ELISA. In each carcinoma group, serum sFas demonstrated a statistically significant elevation relative to levels in normal controls (P < 0.0001). Levels of serum sFas in patients with advanced cancer (FIGO stages III and IV) significantly exceeded those in patients with localized cancer (FIGO stages I and II) or those in normal control subjects (P < 0.0001). We divided the patients into two groups based on the level of serum sFas and examined the relationship between serum sFas levels and survival. No deaths occurred in the groups with cervical and endometrial cancer with a serum sFas level < 1.5 ng/ml. Survival rates in groups with cervical carcinoma, endometrial carcinoma, and ovarian carcinoma with a serum sFas level < 1.5 ng/ml exceeded those in groups with sFas levels of 21.5 ng/ml (P < 0.001, P = 0.128, and P = 0.012, respectively). Proportional hazard models demonstrated that serum sFas level was a statistically significant factor (P = 0.0196) for survival, as well as histological grade (P = 0.0168) in ovarian carcinoma.
Fas-Fas配体系统在细胞毒性T淋巴细胞（CTL）和自然杀伤细胞介导的细胞凋亡中起重要作用。细胞凋亡的抑制有助于致癌作用，以及对化疗和放疗的抗性。由可变mRNA剪接产生的循环可溶性Fas（sFas）可拮抗细胞表面Fas功能。我们通过使用Fas特异性酶联免疫吸附测定（ELISA），研究了64例妇科恶性肿瘤患者（28例宫颈癌、18例子宫内膜癌和18例卵巢癌）和24名健康女性供体的sFas水平。在每个癌症组中，血清sFas相对于正常对照水平显示出统计学上的显著升高（P < 0.0001）。晚期癌症（国际妇产科联盟（FIGO）III和IV期）患者的血清sFas水平显著超过局限性癌症（FIGO I和II期）患者或正常对照受试者的水平（P < 0.0001）。我们根据血清sFas水平将患者分为两组，并检查血清sFas水平与生存率之间的关系。血清sFas水平<1.5 ng/ml的宫颈癌和子宫内膜癌组未发生死亡。血清sFas水平<1.5 ng/ml的宫颈癌、子宫内膜癌和卵巢癌组的生存率超过sFas水平≥1.5 ng/ml组（分别为P < 0.001、P = 0.128和P = 0.012）。比例风险模型表明，血清sFas水平是生存的统计学显著因素（P = 0.0196），也是卵巢癌组织学分级的统计学显著因素（P = 0.0168）。
