【文献解读】BCG治疗期间非肌肉浸润性膀胱癌的系统性体液反应:少即是多
2017/8/3 创新医学网
文章来源:欧尔意 OAE 微信号
作者:Sofina
原文出处
Calais da Silva FM, Videira PA, Ligeiro D, Cabral MG, Sylvester R, Calais da Silva FE, Trindade H. Systemic humoral responses of non-muscle-invasive bladder cancer during BCG treatment: less is more. J Cancer Metastasis Treat 2017;3:116-26.
DOI:10.20517/2394-4722.2017.25.
摘要
目的:卡介苗(BCG)灌注是非肌肉浸润性膀胱癌的主要辅助治疗方法。然而,在接受BCG治疗后的第一年里,有三分之一的患者会复发。本研究的目的是确定生物标志物来预测对BCG治疗的反应。方法:对58例接受BCG治疗的患者的血细胞进行基因表达分析,通过连续6周灌注治疗,然后在第3个月、6个月、9个月和第12个月进行灌注治疗。细胞因子肿瘤坏死因子(TNF)-α,白细胞间素(IL)-10,干扰素(IFN)-γ,IL-1β, IL-2, IL-4, 和 IL-6;趋化因子CCL2、CCL3、CCL8、CXCL9和IP-10以及细胞毒性的介质CTLA4、Fas-L、Perf、GNLY、NOS2A和HMOX-1都在第1周和第6周灌注治疗前和24小时后被分析,并对其进行了快速评估(24小时内)和治疗带来的长期变化。结果:BCG灌注导致了IL-1β、TNF-α和IL-10基因的快速表达。与复发患者相比,在一年内无复发的患者在第1周显示IL-1β的表达明显降低,在第6周的IFN-γ,HMOX-1和GNLY的表达较少。HMOX-1和GNLY是独立的预测生物标志物,而分别大于等于临界值110和13.0 ‰mRNA时,被认为是有害因素。有两个HMOX-1和GNLY因子的患者其复发风险最高(66.7%)。结论:评估免疫调节剂在血液中的表达允许建立预测性临界值,并确定BCG治疗后患者复发的概率。
关键词:膀胱癌,卡介苗,免疫调节分子,多变量分析。
Aim: Intravesical Bacille Calmette-Guérin (BCG) is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer. However, one third of the patients on BCG regimen relapse within the first year of treatment. This study aimed at identifying biomarkers to predict response to BCG treatment. Methods: Gene expression was analyzed in blood cells of 58 patients treated with BCG through six consecutive weekly instillations and then at month 3, 6, 9, and 12. Cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-10, interferon (IFN)-γ, IL-1β, IL-2, IL-4, and IL-6; chemokines CCL2, CCL3, CCL8, CXCL9, and IP-10; and mediators of cytotoxicity CTLA4, Fas-L, Perf, GNLY, NOS2A, and HMOX-1 were analyzed before the 1st and the 6th week instillation and 24 h after to assess fast (within 24 h) and prolonged changes resulting from treatment. Results: BCG instillation led to fast-increased expression of IL-1β, TNF-α, and IL-10genes. When compared to relapsing patients, patients with no relapses within one year showed significantly lower expression of IL-1β at 1st week and less IFN-γ, HMOX-1, and GNLY at week 6. HMOX-1 and GNLY were independent predictive biomarkers, and values above the cut-off ≥ 110 and ≥ 13.0 ‰ mRNA, respectively, were considered prejudicial factors. Patients with two HMOX-1 and GNLY factors had highest (66.7%) relapsing risk. Conclusion: Assessing immunomodulators’ expression in blood allows the establishment of predictive cut-off values and identification of probabilities for patients’ relapses after BCG treatment.
Key words: Bladder cancer, Bacille Calmette-Guérin, immunomodulatory molecules, multivariate analysis.
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