Bioinformatic assessment of the relationship between breast cancer and autophagy-related protein Ambra1 mutation

INTRODUCTION: Autophagy protein 1, regulated by Beclin 1 (Ambra1), promotes tumor formation and development by modulating autophagy. Therefore, in situ intervention in autophagy is a promising new strategy for tumor therapy. We aimed to evaluate the possible effects of changes in the Ambra1 gene on breast cancer (BC) treatment in the BRCA cohort.
METHODS: The gene profile of a total of 996 patients with BC was examined using data obtained from the Cancer Genome Atlas database via cBioPortal. The effects of mutations on proteins were examined by scoring the Polymorphism Phenotyping v2, Mutation Assessor, and Sorting Intolerant from Tolerant databases. The association of genes with other genes was determined with the STRING database. Kaplan-Meier Plot database was used by evaluating the overall survival (OS). The promoter methylation was evaluated by the UALCAN database.
RESULTS: Eleven mutations were detected. Four of these mutations were truncated proteins. Ambra1 tissue expression levels were upregulated compared to healthy tissue in the BRCA cohort; this was not statistically significant (p>0.05).
Decreased Ambra1 expression levels were associated with a shorter OS (p=0.038). Ambra1 promoter region hypermethylation was significant in the BRCA cohort compared to healthy tissue (p<0.001).
DISCUSSION AND CONCLUSION: To our best knowledge, our study is the first to examine the relationship between BC and Ambra1 using bioinformatic tools. Ambra1 may be a candidate target molecule within the treatment strategy due to the mutations evaluated in the BRCA cohort, hypermethylation status, and the association of Ambra1 with shorter OS. However, these situations need to be confirmed by further studies.