Zhao Ming, Zhang Jing, Chen Siyu, Wang Yuqi, Tian Qing
Department of Thoracic Surgery, The General Hospital of the People's Liberation Army, Beijing, 100853, People's Republic of China.
Department of Thoracic Surgery, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, People's Republic of China.
Cancer Manag Res. 2020 Aug 4;12:6755-6766. doi: 10.2147/CMAR.S255072. eCollection 2020.
This study was done to investigate the influence of -gene polymorphism on the prognosis and safety of postoperative patients with non-small cell lung cancer (NSCLC) who had received platinum-based adjuvant chemotherapy.
A total of 289 postoperative patients with NSCLC who had received platinum-based adjuvant chemotherapy from January 2012 to June 2019 participated in this study. Recurrence status and adverse reactions were documented during adjuvant chemotherapy. Overall survival (OS) data were obtained through telephone follow-up. DNA extracted from hematologic specimens was genotyped for -gene polymorphism. Associations between genotype status and prognosis were assessed using Kaplan-Meier survival analysis, and multivariate adjustment was performed using Cox regression analysis.
Median disease-free survival of the 289 patients with NSCLC was 3.3 years and median OS 4.9 years. With regard to the gene polymorphism, only rs822336 was of clinical significance in the subsequent analysis. The minor-allele frequency of rs822336 was 0.21, and distribution of the three genotypes was in accordance with the Hardy-Weinberg equilibrium (=0.807). Survival analysis according to genotype status suggested that median disease-free survival of patients with GG and GC/CC genotypes was 2.8 and 4.1 years, respectively (=0.01). Median OS of patients with GG and GC/CC genotypes was 4.1 and 5.4 years, respectively (=0.008). However, the safety analysis failed to find a significant association between the polymorphism and adverse reactions. Interestingly, expression analysis of RNA extracted from peripheral blood mononuclear cells indicated that -mRNA expression of patients with the GG genotype was significantly higher than for the GC/CC genotype (<0.001).
The prognosis of postoperative patients with NSCLC who have received platinum-based adjuvant chemotherapy may be influenced by the rs822336 polymorphism through mediation of the mRNA expression of .
本研究旨在探讨基因多态性对接受铂类辅助化疗的非小细胞肺癌(NSCLC)术后患者预后及安全性的影响。
共有289例在2012年1月至2019年6月期间接受铂类辅助化疗的NSCLC术后患者参与本研究。在辅助化疗期间记录复发情况和不良反应。通过电话随访获得总生存(OS)数据。从血液标本中提取的DNA进行基因多态性基因分型。使用Kaplan-Meier生存分析评估基因型状态与预后之间的关联,并使用Cox回归分析进行多变量调整。
289例NSCLC患者的中位无病生存期为3.3年,中位OS为4.9年。关于该基因多态性,在后续分析中只有rs822336具有临床意义。rs822336的次要等位基因频率为0.21,三种基因型的分布符合Hardy-Weinberg平衡(P = 0.807)。根据基因型状态进行的生存分析表明,GG和GC/CC基因型患者的中位无病生存期分别为2.8年和4.1年(P = 0.01)。GG和GC/CC基因型患者的中位OS分别为4.1年和5.4年(P = 0.008)。然而,安全性分析未发现该多态性与不良反应之间存在显著关联。有趣的是,从外周血单个核细胞中提取的RNA的表达分析表明,GG基因型患者的mRNA表达明显高于GC/CC基因型患者(P < 0.001)。
接受铂类辅助化疗的NSCLC术后患者的预后可能通过基因的mRNA表达介导受rs822336多态性的影响。