Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5589668 | Gene | 2017 | 30 Pages |
Abstract
Autophagy-related genes (ATGs) play a critical role in the development of various diseases including cancer. However, the role of ATGs in breast cancer survival remains unclear. This study aims to investigate whether genetic variants in core ATGs are correlated with the prognosis of breast cancer. A total of 14 potentially functional variants in core ATGs were genotyped in 790 breast cancer patients. The association of each variant with breast cancer-specific survival was evaluated by log-rank test and Cox regression model. In silico analysis was also performed to evaluate the potential function of selected variants. We found that one variant in ATG7 rs8154 (AÂ >Â G) was significantly associated with breast cancer-specific survival after adjusted for age and clinical stage (HRÂ =Â 1.61, 95% CI: 1.12-2.31, PÂ =Â 0.010). Stratified analysis showed that the prognostic role of rs8154 was significant in subgroups of elder age, elder menarche age, and postmenopausal status (all PÂ <Â 0.001). Interaction effects were also detected between rs8154 and these grouping variables. In silico analysis revealed that rs8154 was annotated to be expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets (both PÂ <Â 0.05). In addition, upregulated expression of ATG7 in breast cancer tissues was observed and is significantly associated with poorer overall survival (log-rank PÂ =Â 0.015), poorer relapse free survival (log-rank PÂ =Â 0.017), and poorer distant metastasis free survival (log-rank PÂ =Â 0.034) in different datasets. Summarily, ATG7 variant rs8154 represents a novel prognostic marker for breast cancer patients, which may shed light on clinical risk stratification and therapeutic decision making.
Keywords
GTExHER2RNA-Seq by Expectation Maximizationhuman epithelial growth factor receptor 2RSEMMAFTCGAHWEeQTLATG7ATGsAutophagyThe cancer genome atlasExpression quantitative trait locigenotype-tissue expressionHardy–Weinberg equilibriumBreast cancerLinkage disequilibriumconfidence intervalsminor allele frequencyhazard ratiosVariantprognosisautophagy-related genesESESEstrogen receptor
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Authors
Jing Zhou, Dong Hang, Yue Jiang, Jiaping Chen, Jing Han, Wen Zhou, Guangfu Jin, Hongxia Ma, Juncheng Dai,