, a P53-downstream Gene, is Associated with Suppression of Breast Cancer Cell Proliferation and Better Survival

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2022 Jan 12

PMID 35018242

Authors

Manabu Futamura

Yoshihisa Tokumaru

Kazuaki Takabe

Hirofumi Arakawa

Yoshimi Asano

Ryutaro Mori

Junichi Mase

Akira Nakakami

Kazuhiro Yoshida

Affiliations

Soon will be listed here.

Abstract

Mitochondria-eating protein (; also known as ), a p53-downstream gene, is involved in mitochondrial quality control (MQC). Enforced MIEAP expression induces caspase-dependent cell death in vitro, and impairment of the p53/-regulated MQC pathway is frequently observed in breast cancer (BC), resulting in poor disease-free survival (DFS). To investigate the clinical significance of in BC, we identified 2,980 patients from two global, large-scale primary BC cohorts: the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1,904) and the Cancer Genome Atlas (TCGA; n=1,076). We divided patients in each cohort into high and low groups based on median gene expression levels and analyzed the association between expression and clinical outcomes. Compared with normal tumors, expression was significantly downregulated in all patients with -mutant BC regardless of subtype. expression was negatively correlated with expression. Gene set enrichment analysis demonstrated that cell cycle- and proliferation-associated gene sets were significantly enriched in -low tumors compared to -high tumors. Patients with -high luminal subtype were associated with significantly longer DFS than those with -low luminal tumors in both cohorts, whereas significantly longer overall survival was observed only in the METABRIC cohort, which has roughly double the number of samples. These results indicated that the mechanistic role of is clinically relevant in the two independent cohorts. This is the first study to use large cohorts to demonstrate the association between expression and survival in patients with luminal subtype BC.

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