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. 2022 May 24;13(1):34.
doi: 10.1007/s12672-022-00497-y.

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

Mmadili N Ilozumba  1 , Song Yao  2 , Adana A M Llanos  3 , Angela R Omilian  2 , Weizhou Zhang  4 , Susmita Datta  5 , Chi-Chen Hong  2 , Warren Davis  2 , Thaer Khoury  6 , Elisa V Bandera  7 , Michael Higgins  8 , Christine B Ambrosone  2 , Ting-Yuan David Cheng  9   10
Affiliations

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

Mmadili N Ilozumba et al. Discov Oncol. .

Abstract

Background: Aberrant 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.

Methods: Surgical tumor tissue blocks were collected from 367 newly diagnosed breast cancer patients (190 Black and 177 White). Gene expression of AKT1, EIF4EBP1, MTOR, RPS6KB2, and TSC1 were 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.

Results: Compared to White women, Black women had relative under-expression of AKT1 (log2 fold-change = - 0.31, 95% CI - 0.44, - 0.18) and RPS6KB2 (log2 fold-change = - 0.11, 95% CI - 0.19, - 0.03). Higher vs. lower tumor grade was associated with relative over-expression of EIF4EBP1 and RPS6KB2, but with lower expression of TSC1. Compared to luminal tumors, triple-negative tumors had relative under-expression of TSC1 (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 the AKT1 and RPS6KB2 locus between Black and White women.

Conclusions: Over-expression of RPS6KB2 and EIF4EBP1 and under-expression of TSC1 might be indicators of more aggressive breast cancer phenotypes. Differential expression of AKT1 and RPS6KB2 by race warrants further investigation to elucidate their roles in racial disparities of treatment resistance and outcomes between Black and White women with breast cancer.

Keywords: Breast cancer; Clinicopathological characteristics; Gene expression; Race; mTOR.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
mTOR signaling pathway in cancer (revised from Zoncu et al. Nature Reviews. 2011 12:21–35). 4E-BP1 eukaryotic translation initiation factor 4E-binding protein 1; Akt protein kinase B; HIF1α hypoxia-inducible factor 1α; eIF-4E eukaryotic translation initiation factor 4E; mTORC1 mammalian Target of Rapamycin complex 1; mTORC2 mammalian Target of Rapamycin complex 2; Rheb Ras Homologue enriched in brain; S6K1/2 p70 ribosomal S6 kinase 1 and 2; SGK serum- and glucocorticoid-regulated kinase; SREBP1 sterol regulatory element binding protein 1c; TSC1/2 tuberous sclerosis protein 1 and 2
Fig. 2
Fig. 2
mTOR gene expression levels among Black women vs. White women, stratified by molecular subtypes. A Luminal, p-value = 0.0003; HER2+, p-value = 0.1696; Triple-negative, p-value = 0.0028, B Luminal, p-value = 0.8275; HER2+, p-value = 0.8599; Triple-negative, p-value = 0.9744, C Luminal, p-value = 0.7066; HER2+, p-value = 0.3314; Triple-negative, p-value = 0.8613, D Luminal, p-value = 0.0348; HER2+, p-value = 0.3720; Triple-negative, p-value = 0.1132, E Luminal, p-value = 0.7842; HER2+, p-value = 0.6807; Triple-negative, p-value = 0.3711
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