Overexpression of CDC25A, AURKB, and TOP2A Genes Could Be an Important Clue for Luminal A Breast Cancer.

Abstract

Objective: Breast cancer (BC) is highly heterogeneous and one of the most common cancers. Luminal A (LUM A) is a subtype of BC with a better prognosis than other BC subtypes. The molecular mechanisms underlying the initiation and progression of the LUM A subtype are still unclear. Big data generated from microarray and sequencing systems can be re-analyzed, especially with the help of various in silico tools developed in recent years, and made applicable for in vitro and in vivo research. This work aimed to identify genes that may play a role in the progression of LUM A subtype of BC using both computational and laboratory-based methods.

Materials and methods: Overlapping genes associated with BC were identified from the The Cancer Genome Atlas database, GSE233242, GSE100925 geodata sets, and the geneshot tool. The network functional analysis between overlapping genes was determined with STRING 12.0. Expression levels of overlapping genes in BC were investigated with the TNMplot (https://tnmplot.com/analysis/) in silico tool. The effect of overlapping genes on the overall survival of LUM A cancer patients was defined using the Kaplan-Meier plotter tool. Expressions of genes identified using bioinformatics data were investigated via quantitative real-time -polymerase chain reaction (qRT-PCR) in LUM A tumor and adjacent tissue samples. The data were evaluated using the t-test. Both the sensitivity and specificity of selected genes have been determined using the receiver operating characteristic curve.

Results: In silico investigation showed that eleven genes were possibly associated with BC. Among them CDC25A, AURKB, and TOP2A were considerably increased in LUM A samples according to qRT-PCR results. An overall survival analysis also showed that overexpression of these three genes could reduce the overall survival of LUM A patients.

Conclusion: The genes CDC25A, AURKB, and TOP2A may play crucial functions in LUM A pathogenesis. Therapeutic strategies that diminish the expression of these connected genes may enhance the prognosis of LUM A patients.