mTOR pathway gene expression in association with race and clinicopathological characteristics in Black and White breast cancer patients

Abstract

AbstractBackgroundAberrant activation of the mammalian Target of Rapamycin (mTOR) pathway has been linked to obesity and endocrine therapy resistance, factors that may contribute to Black-White disparities in breast cancer outcomes. We evaluated associations of race and clinicopathological characteristics with mRNA expression of key mTOR pathway genes in breast tumors.MethodsSurgical tumor tissue blocks were collected from 367 newly diagnosed breast cancer patients (190 Black and 177 White). Gene expression ofAKT1,EIF4EBP1,MTOR,RPS6KB2, andTSC1were quantified by NanoString nCounter. Differential gene expression was assessed using linear regression on log2-transformed values. Gene expression and DNA methylation data from TCGA were used for validation and investigation of race-related differences.ResultsCompared to White women, Black women had relative under-expression ofAKT1(log2 fold-change = − 0.31, 95% CI − 0.44, − 0.18) andRPS6KB2(log2 fold-change =− 0.11, 95% CI − 0.19, − 0.03). Higher vs. lower tumor grade was associated with relative over-expression ofEIF4EBP1andRPS6KB2, but with lower expression ofTSC1. Compared to luminal tumors, triple-negative tumors had relative under-expression ofTSC1(log2 fold-change = − 0.42, 95% CI − 0.22, − 0.01). The results were similar in the TCGA breast cancer dataset. Post-hoc analyses identified differential CpG methylation within theAKT1andRPS6KB2locus between Black and White women.ConclusionsOver-expression ofRPS6KB2andEIF4EBP1and under-expression ofTSC1might be indicators of more aggressive breast cancer phenotypes. Differential expression ofAKT1andRPS6KB2by race warrants further investigation to elucidate their roles in racial disparities of treatment resistance and outcomes between Black and White women with breast cancer.