Clinical significance of BIM deletion polymorphism in chemoradiotherapy for non-small cell lung cancer.
Clinical significance of BIM deletion polymorphism in chemoradiotherapy for non-small cell lung cancer.
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DOI：
10.1111/cas.14711
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发表时间：
2021-01
期刊：
影响因子：
5.7
通讯作者：
Hattori N
中科院分区：
文献类型：
--
作者：
Wakabayashi Y;Masuda T;Fujitaka K;Nakashima T;Okumoto J;Shimoji K;Nishimura Y;Yamaguchi K;Sakamoto S;Horimasu Y;Miyamoto S;Iwamoto H;Ohshimo S;Hamada H;Hattori N
局部晚期非小细胞肺癌（NSCLC）的标准治疗是放化疗（CRT），然后是抗程序性细胞死亡配体1（抗PD-L1）治疗。BIM缺失多态性诱导EGFR突变NSCLC患者中表皮生长因子（EGFR）酪氨酸激酶抑制剂引起的细胞凋亡抑制。我们的目的是检查BIM多态性对NSCLC患者CRT和抗PD-L1/PD-1治疗的影响。这项回顾性研究纳入了1994年4月至2019年10月期间在东广岛医疗中心和广岛大学医院接受治疗的1312例不可切除NSCLC患者，我们招募了接受CRT或卡铂+紫杉醇或顺铂+长春瑞滨化疗或抗PD‐L1/PD‐1治疗的患者。在1312例患者中，分别有88、80和74例接受CRT、化疗和抗PD-L1/PD-1治疗，其中17.0%、15.2%和17.6%的患者显示BIM多态性。在接受CRT的患者中，BIM缺失的患者的无进展生存期显著短于无BIM缺失的患者。在多变量分析中，BIM多态性是抗肿瘤效果差的独立因素。在化疗和抗PD-L1/PD-1治疗组中未观察到这些结果。在体外实验中，在NSCLC细胞系中使用小干扰RNA抑制BIM表达显示出放射后显著抑制的抗肿瘤作用和细胞凋亡，而不是化疗。总之，我们发现BIM多态性是接受CRT（特别是放疗）的NSCLC患者抗肿瘤效应的不良预测因素。在BIM多态性患者中实施CRT时，我们应考虑后续治疗，记住CRT可能不足。我们发现，与无BIM多态性的患者相比，接受CRT治疗的NSCLC患者的无进展生存期和总生存期显著缩短。我们的研究结果表明，BIM多态性与CRT患者的放疗疗效相关，但与化疗无关。
The standard treatment for locally advanced non‐small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti‐programmed cell death‐ligand 1 (anti‐PD‐L1) treatment. BIM deletion polymorphism induces the suppression of apoptosis resulting from epidermal growth factor (EGFR)‐tyrosine kinase inhibitors in EGFR‐mutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on CRT and anti‐PD‐L1/PD‐1 treatment in NSCLC patients. In this retrospective study of 1312 patients with unresectable NSCLC treated at Higashi‐Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and October 2019, we enrolled those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti‐PD‐L1/PD‐1 treatment. Of 1312 patients, 88, 80, and 74 underwent CRT, chemotherapy, and anti‐PD‐L1/PD‐1 treatment, respectively, and 17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients receiving CRT, the progression‐free survival was significantly shorter in those with BIM deletion than in those without. In the multivariate analyses, BIM polymorphism was an independent factor of poor anti‐tumor effects. These results were not observed in the chemotherapy and anti‐PD‐L1/PD‐1 treatment groups. In in vitro experiments, BIM expression suppression using small interfering RNA in NSCLC cell lines showed a significantly suppressed anti‐tumor effect and apoptosis after irradiation but not chemotherapy. In conclusion, we showed that BIM polymorphism was a poor‐predictive factor for anti‐tumor effects in NSCLC patients who underwent CRT, specifically radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we should consider subsequent treatment, keeping in mind that CRT may be insufficient. We showed that progression‐free survival and overall survival durations were significantly shorter in the CRT‐treated NSCLC patients with BIM polymorphism than in those without. Our findings indicate that BIM polymorphism is associated with the efficacy of radiotherapy but not chemotherapy in patients with CRT.
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影响因子：
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作者：
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