2021 年第 3 期 第 16 卷

血浆转化生长因子β1水平在预测肺癌患者放疗后近期疗效中的作用及相关机制分析

The role of plasma transforming growth factor-β1 level in predicting the short-term efficacy of radiotherapy in patients with lung cancer and its related mechanisms

作者：葛飞1黄向东1路杰2

英文作者：Ge Fei1 Huang Xiangdong1 Lu Jie2

单位：1甘肃省庆阳市人民医院胸心外科745000；2甘肃省庆阳市镇原县中医院普外科744500

英文单位：1Department of Cardiothoracic Surgery Qingyang People′s Hospital Gansu Province Qingyang 745000 China; 2Department of General Surgery Zhenyuan County Traditional Chinese Medicine Hospital Gansu Province Qingyang 744500 China

关键词：肺癌；放疗；转化生长因子β1；淋巴细胞亚群；磷脂酰肌醇-3-激酶-蛋白激酶B-哺乳动物雷帕霉素靶蛋白通路

英文关键词：Lungcancer;Radiotherapy;Transforminggrowthfactor-β1;Lymphocytesubsets;Phosphatidylinositol3-kinase-protenkinaseB-mammaliantargetofrapamycinpathway

• 摘要：

• 目的 探讨血浆转化生长因子β1(TGF-β1)水平在预测肺癌患者放疗后近期疗效中的作用及相关机制。方法 选取2016年6月至2017年6月在甘肃省庆阳市人民医院接受胸部调强放疗的肺癌患者78例。分别于放疗前、放疗2周和4周、放疗结束后6周采集血液标本检测血浆TGF-β1和外周血淋巴细胞亚群水平以及磷脂酰肌醇-3-激酶(PI3K)-蛋白激酶B(Akt)-哺乳动物雷帕霉素靶蛋白(mTOR)通路相关蛋白表达情况。分析放疗前后血浆TGF-β1水平与疗效的关系；分析放疗期间血浆TGF-β1与外周血淋巴细胞亚群水平的相关性。结果 放疗2、4周和放疗结束后6周，治疗有效者TGF-β1水平均明显低于治疗无效者（均P＜0.05）。放疗2、4周和放疗结束后6周患者血浆TGF-β1水平与同时点CD+4细胞和CD+4/CD+8比值均呈明显负相关，与CD+8细胞均呈明显正相关（均P＜0.01）。放疗4周和放疗结束后6周磷酸化mTOR（p-mTOR）蛋白相对表达量分别为（3.25±0.72）、（1.76±0.54），磷酸化Akt（p-Akt）蛋白相对表达量分别为（1.95±0.64）、（1.02±0.38），均明显低于放疗前和放疗2周［p-mTOR：（5.91±1.15）、（6.14±1.80），p-Akt：（8.36±1.47）、（7.51±1.13）］（均P＜0.05）。结论 肺癌患者放疗后TGF-β1水平降低者近期疗效较好；其机制可能为TGF-β1水平降低通过提升T淋巴细胞水平来抑制Akt/mTOR磷酸化，降低PI3K-Akt-mTOR信号通路活性，增强机体抗肿瘤免疫反应。

• Objective To investigate the role of plasma transforming growth factor-β1(TGF-β1) level in predicting the short-term efficacy of radiotherapy in lung cancer patients and its related mechanism. Methods From June 2016 to June 2017, 78 patients with lung cancer who received chest intensity-modulated radiotherapy in Qingyang People′s Hospital, Gansu Province were prospectively selected. Blood samples were collected before radiotherapy, 2 and 4 weeks after radiotherapy, and 6 weeks after completion of radiotherapy to detect the levels of plasma TGF-β1 and peripheral blood lymphocyte subsets, and the expressions of phosphatidylinositol 3-kinase (PI3K)-proten kinase B(AKT)-mammalian target of rapamycin(mTOR) pathway related proteins. The relationship between the level of plasma TGF-β1 and the curative effect before and after radiotherapy was analyzed; the correlation between plasma TGF-β1 and peripheral blood lymphocyte subsets levels during radiotherapy was analyzed. Results At 2 and 4 weeks after radiotherapy and 6 weeks after completion of radiotherapy, the levels of TGF-β1 in patients with effective treatment were significantly lower than those in patients with ineffective treatment (all P＜0.05). At 2 and 4 weeks after radiotherapy and 6 weeks after completion of radiotherapy, the levels of plasma TGF-β1 were negatively correlated with CD+4 cells and the ratio of CD+4/CD+8 at the same time points, but positively correlated with CD+8 cells (all P＜0.01). At 4 weeks after radiotherapy and 6 weeks after completion of radiotherapy, the relative expression levels of phosphorylated(p)-mTOR and p-Akt were （3.25±0.72）,（1.76±0.54） and （1.95±0.64）, （1.02±0.38）, respectively. Those were significantly lower than those before and 2 weeks after radiotherapy［p-mTOR：（5.91±1.15）, （6.14±1.80）;p-Akt：（8.36±1.47）, （7.51±1.13）］（all P＜0.05）. Conclusions The short-term curative effect of patients with lung cancer is better when the level of TGF-β1 decreases after radiotherapy. The mechanism may be that the decrease of TGF-β1 level can increase the level of T lymphocyte, inhibit the phosphorylation of Akt/mTOR, reduce the activity of PI3K-Akt-mTOR signaling pathway and enhance the body′s anti-tumor immune response.