The differential expression of Promyelocytic Leukemia (PML) and retinoblastoma (RB1) genes in breast cancer

Breast cancer consists of various subtypes like Her2+, ER/PR+Her2-, ER/PR+Her2+, TNBCs (Triple-Negative Breast Cancers), TPBCs (Triple-Positive Breast Cancers), etc., according to hormonal receptors and Her2 profile. Among these, TNBCs have limited therapeutic interventions, due to lack of receptors for ER, PR and Her2. Apart from BRCA1 and BRCA2, there are certain tumor suppressors and/or oncogenes (PML and RB1) influencing breast cancer, but the precise implication of these genes and their correlation is still not clearly understood. These genes play pivotal role in cell cycle regulation, proliferation, differentiation, survival, and apoptosis. Thus, we sought to identify the role of PML and RB1, and their correlation in breast cancer especially in TNBCs. Data demonstrated that 17% were TNBCs, interestingly among these cases, 72% showed remarkable upregulation of PML and downregulation of RB1; whereas 14% cases showed downregulation of PML and RB1, and 14% cases showed loss of expression of PML and RB1. To further validate our results, we included the data from METABRICS and TCGA datasets. Interestingly, our data showed good concordance with METABRICS and TCGA data showing upregulation of PML and downregulation of RB1 in TNBCs. In addition, we also checked the survivability effect of PML and RB1 through Kaplan-Meier plotter and observed that upregulation of PML and down regulation of RB1 decreases recurrence-free survivability in TNBC cases. Overall, the data suggests a plausible role of PML and RB1 genes in breast cancer patients particularly in TNBCs, where treatment options are limited compared to the other subtypes of breast cancer cases.