2023 年第 11 期 第 18 卷

克唑替尼靶向治疗间变性淋巴瘤激酶与C-ros原癌基因1-受体酪氨酸激酶融合基因阳性晚期非小细胞肺癌患者的效果分析

The effect of targeted therapy of crizotinib on advanced non-small cell lung cancer patients with anaplastic lymphoma kinase and C-ros oncogene 1-receptor tyrosine kinase fusion gene positive

作者：李莉赵振慧李妍马小平刘丹李冰玉赵兵

英文作者：Li Li Zhao Zhenhui Li Yan Ma Xiaoping Liu Dan Li Bingyu Zhao Bing

单位：新疆医科大学附属肿瘤医院肿瘤内科，乌鲁木齐830011

英文单位：Department of Oncology Cancer Hospital Affiliated to Xinjiang Medical University Urumqi 830011 China

关键词：非小细胞肺癌；克唑替尼；间变性淋巴瘤激酶；C-ros原癌基因1-受体酪氨酸激酶；融合基因；靶向治疗

英文关键词：Non-smallcelllungcancer;Crizotinib;Anaplasticlymphomakinase;C-rosoncogene1-receptortyrosinekinase;Fusiongene;Targetedtherapy

• 摘要：

• 目的  分析克唑替尼靶向治疗间变性淋巴瘤激酶（ALK）、C-ros原癌基因1-受体酪氨酸激酶（ROS1）融合基因阳性晚期非小细胞肺癌（NSCLC）患者的效果。方法  选取2020年6月至2022年6月来新疆医科大学附属肿瘤医院就诊的123例ALK阳性（ALK组）、15例ROS1阳性（ROS1组）晚期NSCLC患者为研究对象，所有患者均给予克唑替尼治疗，并纳入同期来本院进行健康检查的50名健康志愿者作为对照组。比较对照组入组时以及ALK组和ROS1组治疗前及治疗1、3个月后的循环肿瘤细胞（CTCs）、循环肿瘤DNA（CTDNA）、循环血液外泌体微小RNA-145（miR-145）、miR-200水平及ALK、ROS1阳性率。结果  治疗前ALK组和ROS1组CTCs和CTDNA水平均高于对照组，差异均有统计学意义（均P<0.05）。治疗1、3个月后ALK组和ROS1组患者的CTCs水平逐渐降低，CTDNA水平先升高后降低，与治疗前比较差异均有统计学意义［ALK组：（7.84±0.91）、（5.17±0.87）比（11.53±3.52），（7.19±1.13）、（4.02±0.95）比（5.49±1.17）；ROS1组：（8.05±1.16）、（5.86±0.92）比（12.71±4.08），（7.42±1.24）、（4.55±1.14）比（5.66±1.32）］（均P<0.05）。治疗前ALK组和ROS1组miR-145水平均低于对照组、miR-200水平均高于对照组，差异均有统计学意义（均P<0.05）。治疗1、3个月后ALK组和ROS1组患者的miR-145水平均升高，miR-200水平均降低，与治疗前比较差异均有统计学意义（均P<0.05）。对照组ALK、ROS1阳性率均为0。治疗1、3个月后ALK组和ROS1组患者的ALK、ROS1阳性率均低于治疗前，差异均有统计学意义（均P<0.05）。结论  克唑替尼靶向治疗ALK、ROS1融合基因阳性晚期NSCLC能够通过调节患者CTCs、CTDNA、miR-145、miR-200水平而降低ALK、ROS1阳性表达率。

• Objective  To analyze the effect of targeted therapy of crizotinib on advanced non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase(ALK) and C-ros oncogene 1-receptor tyrosine kinase (ROS1) fusion gene positive. Methods  Totally 123 ALK positive(ALK group) and 15 ROS1 positive (ROS1 group) patients with advanced NSCLC admitted to Cancer Hospital Affiliated to Xinjiang Medical University from June 2020 to June 2022 were selected as the study subjects. All patients were treated with crizotinib, and 50 healthy volunteers who came to the hospital for health examinations during the same period were included as the control group. Levels of circulating tumor cells(CTCs), circulating tumor DNA(CTDNA), circulating exosomes microRNA-145(miR-145), miR-200, and positive rates of ALK and ROS1 were compared in the ALK group and ROS1 group before treatment, after 1 month and 3 months of treatment and when enrolled in the control group. Results  Before treatment, the levels of CTCs and CTDNA in the ALK group and ROS1 group were higher than those in the control group(all P<0.05). After 1 and 3 months of treatment, the levels of CTCs in the ALK and ROS1 groups gradually decreased, while the levels of CTDNA first increased and then decreased, and there were statistically significant differences compared to before treatment［ALK group: (7.84±0.91), (5.17±0.87) vs (11.53±3.52); (7.19±1.13), (4.02±0.95) vs (5.49±1.17); ROS1 group: (8.05±1.16), (5.86±0.92) vs (12.71±4.08); (7.42±1.24), (4.55±1.14) vs (5.66±1.32)］(all P<0.05). Before treatment, the levels of miR-145 in ALK group and ROS1 group were lower than that in the control group, and the levels of miR-200 were higher than that in the control group(all P<0.05). After 1 and 3 months of treatment, the levels of miR-145 increased and miR-200 decreased in both ALK group and ROS1 group, with statistically significant differences compared to before treatment(all P<0.05). The positive rates of ALK and ROS1 in the control group were both 0. After 1 and 3 months of treatment, the positive rates of ALK and ROS1 in ALK group and ROS1 group were lower than those before treatment(all P<0.05). Conclusion  Crizotinib targeted therapy of advanced NSCLC with ALK and ROS1 fusion gene positive can reduce the positive expression rate of ALK and ROS1 by regulating the levels of CTCs, CTDNA, miR-145 and miR-200 in patients.