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首页> 外文期刊>Chinese journal of cancer >Genetic polymorphisms of autophagy-related gene 5 ( ATG5 ) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy
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Genetic polymorphisms of autophagy-related gene 5 ( ATG5 ) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy

机译：自噬相关基因5（ATG5）rs473543的遗传多态性预测接受蒽环类和/或紫杉烷类辅助化疗的三阴性乳腺癌患者的无病生存期不同

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BackgroundAutophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy. MethodsWe genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom’s MassARRAY system. Kaplan–Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients. ResultsThree genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence ( P =?0.024). Kaplan–Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 ( P =?0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04–2.87; P =?0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele ( P =?0.027). Conclusion ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.
机译：背景自噬在三阴性乳腺癌（TNBC）的化疗耐药性中起着至关重要的作用。因此，自噬相关基因5（ATG5），一种参与自噬调控的必需分子，可能与TNBC的复发有关。这项研究旨在调查ATG5中单核苷酸多态性对以蒽环类和/或紫杉烷类化学疗法治疗的早期TNBC患者无病生存率（DFS）的潜在影响。方法：我们利用序列号的MassARRAY系统对316名接受蒽环类和/或紫杉烷类化疗的TNBC患者进行了ATG5 SNP rs473543基因分型。使用Kaplan–Meier生存分析和Cox比例风险回归分析来分析ATG5 rs473543基因型与TNBC患者临床结局之间的关联。结果在ATG5基因的rs473543中检测到AA，GA和GG三种基因型。在有和没有复发的患者之间，ATG5 rs473543基因型的分布差异显着（P =？0.024）。 Kaplan–Meier生存分析表明，与携带rs473543基因型GG的患者相比，携带ATG5 rs473543的A等位基因的患者复发风险更高，DFS较短（P =？0.034）。此外，在调整了临床因素后，多因素Cox回归分析显示rs473543的AA / GA基因型是DFS的独立预测因子（危险风险[HR]为1.73; 95％置信区间[CI]为1.04-2.87; P =？0.034）。此外，存在A等位基因（AA / GA）的淋巴结阴性患者的DFS比不存在A等位基因的患者短（P =？0.027）。结论ATG5 rs473543基因型可能是预测以蒽环类和/或紫杉类为基础的辅助化疗方案的早期TNBC患者复发的潜在标志物。

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