Abstract
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).ConclusionATG5 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.
Highlights
Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC)
We deduced that autophagy may be closely related with the prognosis of TNBC patients who were treated with anthracycline- and/or taxane-based adjuvant chemotherapy
Details of the clinicopathological characteristics according to autophagy-related gene 5 (ATG5) rs473543 genotypes are summarized, and no significant associations were observed between ATG5 rs473543 genotypes and the clinicopathological characteristics (Table 1)
Summary
Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Autophagy is an evolutionarily conserved catabolic process that is primarily responsible for the removal and recycling of long-lived proteins and damaged organelles to maintain the homeostasis of the cell [9, 10]. It is mainly activated by stress and nutrient deprivation and occurs in both normal and cancer cells [11]. We deduced that autophagy may be closely related with the prognosis of TNBC patients who were treated with anthracycline- and/or taxane-based adjuvant chemotherapy. Given autophagy is a highly regulated process involving a series of key molecules [14], the relationship between these molecules and the diseasefree survival (DFS) of TNBC patients deserves further investigation
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