Department of Medical Oncology, Gazi University Faculty of Medicine, Besevler, Ankara 06500, Turkey.
J Cancer Res Clin Oncol. 2010 Oct;136(10):1471-6. doi: 10.1007/s00432-010-0803-1. Epub 2010 Feb 13.
Bevacizumab-based chemotherapy has become the standard of care in metastatic colorectal cancer (MCRC). We aimed to measure the levels of serum soluble FAS, FASL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and its death receptors DR4 and DR5 in MCRC patients and to define prognostic significance of these parameters in response to bevacizumab in these patients.
The levels of these parameters in serum samples were quantified by a commercially available ELISA kit in 31 MCRC patients before and after 2 cycles of therapy and 25 healthy controls.
Pretreatment sFAS levels in MCRC patients was significantly lower than the levels of controls (p = 0.043). There was no significant difference in sFAS and sFASL levels in MCRC patients before and after bevacizumab-based treatment. There was no significant difference in sFAS/sFASL ratio in MCRC patients before and after treatment and controls. Soluble DR5 levels were significantly higher in pretreatment serum samples compared with controls (p = 0.008). However, pretreatment sTRAIL and sDR4 levels were similar to the levels of controls. There was no significant difference in sTRAIL, sDR4, and sDR5 levels in MCRC patients before and after treatment. When patients were grouped according to treatment response (responders vs. non-responders), post-treatment sFAS/sFASL ratio was significantly lower in responding patients compared with non-responders (p = 0.029). Significant correlations were observed between post-treatment sFASL and sDR4, sFAS and sTRAIL, sTRAIL and sFAS/sFASL ratio, and sFASL and sDR5.
Non-significant changes in apoptotic markers with bevacizumab-based chemotherapy showed that they have no prognostic significance in MCRC patients. Significant change in sFAS/sFASL ratio according to treatment response could be an indicator of chemosensitivity.
贝伐珠单抗为基础的化疗已成为转移性结直肠癌（MCRC）的标准治疗方法。我们旨在测量 MCRC 患者血清可溶性 FAS、FASL、肿瘤坏死因子相关凋亡诱导配体（TRAIL）及其死亡受体 DR4 和 DR5 的水平，并确定这些参数在这些患者对贝伐珠单抗治疗反应中的预后意义。
在 31 例 MCRC 患者接受 2 个周期的治疗前后及 25 例健康对照者中，采用商业上可获得的 ELISA 试剂盒定量检测这些参数在血清样本中的水平。
MCRC 患者治疗前 sFAS 水平明显低于对照组（p = 0.043）。MCRC 患者在接受贝伐珠单抗治疗前后 sFAS 和 sFASL 水平无显著差异。治疗前后 MCRC 患者与对照组的 sFAS/sFASL 比值无显著差异。预处理血清样本中可溶性 DR5 水平明显高于对照组（p = 0.008）。然而，预处理 sTRAIL 和 sDR4 水平与对照组相似。治疗前后 MCRC 患者 sTRAIL、sDR4 和 sDR5 水平无显著差异。根据治疗反应（应答者与非应答者）将患者分组后，与非应答者相比，应答者治疗后 sFAS/sFASL 比值明显降低（p = 0.029）。治疗后 sFASL 与 sDR4、sFAS 与 sTRAIL、sTRAIL 与 sFAS/sFASL 比值、sFASL 与 sDR5 之间均存在显著相关性。
贝伐珠单抗为基础的化疗后凋亡标志物无明显变化表明其对 MCRC 患者无预后意义。根据治疗反应的 sFAS/sFASL 比值的显著变化可能是化疗敏感性的指标。
