Profiles of Expression of SAV1 in Normoxia or Hypoxia Microenviroment are Associated with Breast Cancer Prognosis

Abstract

Background: In breast cancer (BC), hypoxia is associated with poor prognosis. Protein Salvador homolog 1 (SAV1) acts as a tumor suppressor and is downregulated in the cancer cells. However, there is limited data on the expression profile of SAV1 and its importance in BC. It has not been studied to evaluate this phenomenon in a hypoxic microenvironment yet.

Aim: This study aimed to investigate SAV1 expression profiles under normoxia and hypoxia, and the potential of SAV1 in BC prognosis.

Methods: Gene and protein expression analyses were performed using Real-Time quantitative PCR (RT-qPCR) and immunocytochemistry (ICC), respectively, and in silico analyses were performed using The Cancer Genome Atlas (TCGA). The survival curves were constructed using KMplotter.

Results: SAV1 expression was lower in BC samples and tumor cell lines than in normal samples. The SAV1 mRNA levels were reduced in hypoxic estrogen receptor positive (ER⁺) tumors, which were associated with a lower survival probability as compared to normoxic ER⁺ tumors. Furthermore, lower levels of SAV1 were found in advanced cancer stage samples, which are associated with worse survival curves and can be a risk factor for BC.

Conclusions: These data suggest a potential prognostic role of SAV1 in BC, with lower expressions associated with worse prognosis.

Keywords: Breast Cancer; Hypoxia; Prognosis; SAV1; Tumor Suppressor.