PSAT1 gene as a biomarker for targeting triple negative breast cancer in presence of Rapamycin.

The Triple-Negative Breast Cancers (TNBCs) poor survival outcomes are related to not responding to hormonal therapy or targeting HER2 protein. The aim of this study was to introduce a drug among the conventional chemotherapy drugs based on the transcripts of the TNBC patients. The transcriptome of MDA-MB-468 cell line as a TNBC model was analyzed in the presence of 17 common drugs in fifteen GEO datasets. Then, decreased gene lists in the presence of each drug were compared in different subtypes of breast cancer based on TCGA data. The effect of selected drug on survival and apoptosis rates of MDA-MB-468 and MCF-7 cells (as ER+/PR + model) were compared. The outcomes showed that the expression of the decreased gene by Rapamycin among other drugs increased in TNBC subtype compared to the other two subtypes including triple-positive and ER+/PR+. The expression of PSAT1 in TNBC group was significant higher than normal and other subtypes (p ≤ 0.0001), and was introduced as a biomarker in TNBC that its expression was down-regulated by Rapamycin based on in silico studies. In the presence of 3000 µg/mL Rapamycin, there was a sharp decrease in MDA-MB-468 cell viability (p ≤ 0.0001) and a significant increase in apoptosis compared to MCF-7 cells treated with the same concentration of the drug. Moreover, RT-qPCR revealed PSAT1 expression more decreased under Rapamycin-treatment in TNBC cells compared to ER + PR + cells. The results of this study show that Rapamycin is a suitable drug for targeting TNBC based on its transcriptome and biomarker.Supplemental data for this article is available online at.