Abstract:
Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.
摘要:
多药耐药(MDR)通常导致癌症治疗失败,因为癌细胞经常使用ATP结合盒(ABC)转运蛋白排出化疗药物。降低细胞内的药物水平。这项研究调查了ABCB1,ABCC1,ABCC2,ABCC4和ABCG2的临床特征和单核苷酸变异(SNV),以及它们与中枢神经系统肿瘤(CNST)儿科患者死亡率的关系。使用TaqMan探针,实时聚合酶链反应对111个样本中的15个SNP进行了基因分型。使用Cox比例风险模型对患者进行随访直至死亡或最后随访日。在隐性模型中发现rs1045642(ABCB1)之间存在关联(HR=2.433,95%CI1.098-5.392,p=0.029),和协同模型中的ICE方案(HR=9.810,95%CI2.74-35.06,p≤0.001),显性模型(HR=6.807,95%CI2.87-16.103,p≤0.001),和隐性模型(HR=6.903,95%CI2.915-16.544,p=0.038)显著增加了该队列患者的死亡率.在共显性模型(HR=5.35,95%CI1.83-15.39,p=0.002)和显性模型(HR=4.421,95%CI1.747-11.185,p=0.002)中也观察到变异rs3114020(ABCG2)与死亡率之间存在关联。在优势模型中,ICE治疗方案与死亡风险增加之间存在显着关联(HR=6.351,95%CI1.831-22.02,p=0.004,HR=9.571,95%CI2.856-32.07,p≤0.001),显性模型(HR=6.592,95%CI2.669-16.280,p≤0.001),和隐性模型(HR=5.798,95%CI2.411-13.940,p≤0.001)。ABCG2基因中的遗传变异rs3114020和ABCB1基因中的rs1045642以及ICE化疗方案与CNST儿科患者队列中死亡风险增加相关。