血浆中TGF-β1、TNF-α及IL-6动态变化与非小细胞肺癌患者放射性肺炎发生的相关研究

Study of correlation between TGF-β1,TNF-α and IL-6 levels in plasma and radiation pneumonitis in patients with non-small-cell lung cancer

目的探讨接受放疗的非小细胞肺癌(NSCLC)患者血浆中转化生长因子β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平的动态变化与放射性肺炎(RP)发生的关系。方法收集37名接受三维适型放疗的非小细胞肺癌患者信息,分别在放疗前、放疗中、放疗结束、放疗后2周、放疗后4周留取血清学标本,用酶联免疫法测量TGF-β1、TNF-α、IL-6。结果 8名患者(21.6%)发生2级以上RP,放疗前后TGF-β1水平变化与RP的发生及其严重程度相关(r=0.559),TNF-α、IL-6与RP无明显相关。RP组中放疗后4周血清中TGF-β1、TNF-α水平明显高于放疗结束时(P=0.005、P=0.022)。单因素方差分析发现TGF-β1的动态变化与RP的发生风险相关(P<0.001)。结论 TGF-β1的动态变化与RP的发生及其发生的严重程度相关,动态监测其变化有助于早期预测RP发生,从而制定合理的放疗方案。

Objective To correlate the transforming growth factor-β（TGF-β1）,tumor necrosis factor（TNF-α）,interleukin-6（IL-6）levels in non-small-cell lung cancer（NSCLC）patients during radiation therapy（RT）with the occurrence of radiation pneumonitis（RP）.Methods Thirty-seven NSCLC patients who received three-dimensional conformal radiation therapy were evaluated prospectively.Serial blood samples before,in the middle of,at the end of RT and 2 and 4 weeks after RT were analyzed for cytokine by performing enzyme-linked immunosorbent assay.The predictive values of dosimetric factors for RP were evaluated.Results 8 patients（21.6%）had grade≥2 RP.The TGF-β1 level showed a correlation to the RP（r=0.559）.The cytokines TNF-α and IL-6 level was not correlated with the risk of RP.The mean pretreatment TGF-β1,TNFα level did not differ between RP and non-RP groups.However,during the period of radiation treatment,the TGF-β1 level began to increase at the end of RT in the RP group and became significantly higher 4 weeks after RT（P=0.005）.Using an ANOVA model for repeated-measures.There was significant associations between the changes of TGF-β1 during the time course of the RT and the risk of developing RP（P0.001）.Conclusions The results show that the changes of TGF-β1 could be correlated with RP and the incorporation of the biological parameters into the dosimetric data could be useful for predicting symptomatic RP.