GENOMIC AND CLINICAL DATA ANALYSIS OF APE1 PROTEIN, BREAST CANCER STEM CELL PHENOTYPE, AND HYPOXIC TUMOR MICROENVIRONMENT

Abstract

Introduction: Breast cancer (BC) is a heterogeneous disease at cellular and molecular levels. BC tumors present a cellular
subpopulation of breast cancer stem cells (BCSCs) linked with tumor initiation and progression, recurrence, and therapeutic failure. The BCSC is preferentially found in hypoxic areas of the tumor, which are common features of BC and are
significantly associated with worse prognosis. Although hypoxia activates an aggressive BCSC phenotype, the proteins
that perform this molecular crossroad are still unknown. Therefore, finding proteins that performed this crossing would
help define new promisors’ clinical strategies. Apurine/Apyrimidine Endonuclease 1 (APE1) protein has emerged as a new
therapeutic target in cancer treatment and is overexpressed in more aggressive BC tumors. However, the relationship of
APE1 with BCSC considering the hypoxia microenvironment does not exist. Objectives: This study aimed to analyze the
genomic/transcriptomic and clinical data of the APE1, BCSC phenotype, and hypoxic tumors. Methods: Genomic/transcription data and clinical attributes were collected and clustered on the Xena UCSC platform from The Cancer Genome
Atlas (TCGA) BRCA database. Clinical molecular signatures from BCSC and hypoxia-related genes were used to separate
BC patients in high or low expression groups for these genes and they evaluated their clinical data, including survival and
APE1 expressions. Results: Patients with high expression of BCSC-related genes exhibited worse prognosis and overexpression of APE1. Additionally, high expression of hypoxia-related genes was also associated with worse prognosis and exhibited
high levels of APE1. Patients with high expression of BCSC genes also exhibited high levels of hypoxia-related genes. APE1,
BCSC, and hypoxia-related genes were more expressed in BC compared to adjacent normal samples. Conclusion: Data
suggest that APE1 is overexpressed in hypoxia and BCSC phenotype, which are associated with worse prognosis for BC.