Prognostic and predictive implications of sterile alpha motif and HD domain-containing protein 1 (SAMHD1) expression in breast cancer

Abstract

Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a dNTP hydrolase important for intracellular dNTP homeostasis and serves as tumor suppressor and modulator of antimetabolite efficacy in cancer, though largely unexplored in breast cancer (BC). A cohort of patients with early BC (n = 564) with available gene expression data (GEP) was used. SAMHD1 protein expression was assessed by immunohistochemistry performed on tissue microarrays. A large pooled transcriptomic dataset was used for validation (n = 2402). GEP data from the metastatic TEX randomized phase III trial (NCT01433614) were used for SAMHD1 predictive evaluation in response to capecitabine. SAMHD1 protein and mRNA levels were higher in HER2-enriched/HER2+ and basal-like (BL)/ER-/HER2- BC. Both SAMHD1 gene and protein expression were independently associated with favorable outcomes in BL tumors. In the pooled dataset, SAMHD1 gene expression was independently associated with favorable disease-free survival in the entire population and within the BL and HER2-enriched molecular subtypes. In metastatic BC, SAMHD1 mRNA levels were higher in responders receiving capecitabine. In conclusion SAMHD1 gene and protein expression represent promising prognostic biomarkers in BL early BC.