Institute of Medical & Molecular Toxicology, School of Medicine, Institute of Medicine, and School of Public Health, Chung Shan Medical University, Changhua, Taiwan, ROC.
Clin Cancer Res. 2011 Sep 15;17(18):5991-9. doi: 10.1158/1078-0432.CCR-11-0227. Epub 2011 Aug 1.
Fas ligand (FasL) -844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL -844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL -844T/C polymorphism on the clinical outcome of non-small cell lung cancer (NSCLC) remains to be identified.
A total of 385 adjacent normal lung tissues from patients with NSCLC were collected to determine FasL -844T/C polymorphism by PCR-based restriction fragment length polymorphism. FasL mRNA and protein expression in lung tumors were evaluated by real-time PCR and immunohistochemistry. The prognostic value of FasL -844T/C polymorphism on survival and relapse was determined by Kaplan-Meier analysis and Cox proportional hazards models.
The FasL -844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P = 0.008). In addition, patients with the FasL -844CC genotype were more prone to tumor relapse than those with the FasL -844TT+TC genotype (62.1% vs. 37.9%, P = 0.001). Multivariate Cox regression analysis showed that patients with the FasL -844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL -844TT+TC genotype (24.1 vs. 42.8 months for OS, HR = 1.455, P = 0.004; 15.4 vs. 31.4 months for RFS, HR = 1.710, P < 0.001).
FasL -844T/C polymorphism may predict survival and relapse in NSCLC. We suggest that FasL may be a molecular target for immunotherapeutic interventions to improve the clinical outcome of patients with NSCLC. This finding should be validated by another investigative group.
Fas 配体（FasL）-844T/C 多态性（rs763110）已被证明与肺癌风险相关。较高 FasL 表达的 FasL-844CC 被认为通过免疫逃逸促进肿瘤进展。然而，FasL-844T/C 多态性对非小细胞肺癌（NSCLC）的临床结果的影响仍有待确定。
共收集 385 例 NSCLC 患者的癌旁正常肺组织，采用基于 PCR 的限制性片段长度多态性检测 FasL-844T/C 多态性。采用实时 PCR 和免疫组织化学检测肺肿瘤中 FasL mRNA 和蛋白表达。采用 Kaplan-Meier 分析和 Cox 比例风险模型确定 FasL-844T/C 多态性对生存和复发的预后价值。
晚期肿瘤患者 FasL-844CC 基因型的发生率高于早期肿瘤患者（P = 0.008）。此外，FasL-844CC 基因型患者比 FasL-844TT+TC 基因型患者更容易发生肿瘤复发（62.1% vs. 37.9%，P = 0.001）。多变量 Cox 回归分析显示，与 FasL-844TT+TC 基因型相比，FasL-844CC 基因型患者的总生存期（OS）和无复发生存期（RFS）更差（OS：24.1 与 42.8 个月，HR = 1.455，P = 0.004；RFS：15.4 与 31.4 个月，HR = 1.710，P < 0.001）。
FasL-844T/C 多态性可能预测 NSCLC 的生存和复发。我们认为 FasL 可能是免疫治疗干预的分子靶点，以改善 NSCLC 患者的临床结果。这一发现应由另一个研究小组进行验证。
