Abstract
Luminal breast tumors have been classified into A and B subgroups, with the luminal A being associated with a more favorable clinical outcome. Unfortunately, luminal A tumors do not have a universally good prognosis. We used transcriptomic analyses using public datasets to evaluate the differential expression between normal breast tissue and breast cancer, focusing on upregulated genes included in cell cycle function. Association of selected genes with relapse free survival (RFS) and overall survival (OS) was performed using the KM Plotter Online Tool (http://www.kmplot.com). Seventy-seven genes were differentially expressed between normal and malignant breast tissue. Only five genes were associated with poor RFS and OS. The mitosis-related genes GTSE1, CDCA3, FAM83D and SMC4 were associated with poor outcome specifically in Luminal A tumors. The combination of FAM83D and CDCA3 for RFS and GTSE1 alone for OS showed the better prediction for clinical outcome. CDCA3 was amplified in 3.4% of the tumors, and FAM83D and SMC4 in 2.3% and 2.2%, respectively. In conclusion, we describe a set of genes that predict detrimental outcome in Luminal A tumors. These genes may have utility for stratification in trials of antimitotic agents or cytotoxic chemotherapy, or as candidates for direct target inhibition.
Highlights
Breast cancer has been classified in different subtypes by gene expression analyses, and each of these subtypes is associated with different clinical outcomes [1, 2]
Transcriptomic analysis identify upregulated genes linked with cell cycle By comparing gene expression data from normal breast tissue and breast cancers, using a minimum fold change of 4, we identified 136 and 90 dysregulated genes included in the cell cycle function, in basal and non-basal breast cancers, respectively
Mitotic-related genes GTSE, CDCA3, FAM83D and SMC4 are associated with poor outcome
Summary
Breast cancer has been classified in different subtypes by gene expression analyses, and each of these subtypes is associated with different clinical outcomes [1, 2]. The luminal subtype includes those tumors that express the estrogen receptor, and can be targeted with hormonal therapy [1, 3]. This subgroup has been classified as luminal A and B, and these two subtypes are associated with different clinical outcomes [1, 4]. Luminal B tumors are characterized by an increased in proliferation, which is evidenced by elevated levels of Ki67 [5]. Luminal B tumors respond better to cytotoxic chemotherapy than the luminal A subtype
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