Prognostic Significance of DSCC1, a Biomarker Associated with Aggressive Features of Breast Cancer

Abstract

Background and Objectives: Invasive breast cancer (BC) was traditionally investigated visually, and no technique could identify the key molecular drivers of patient survival. However, essential molecular drivers of invasive BC have now been discovered using innovative genomic, transcriptomic, and proteomic methodologies. Nevertheless, few evaluations of the prognostic factors of BC in Saudi Arabia have been performed. Evaluating the biomarkers associated with the development of early-stage BC could help determine the risk of metastasis and guide treatment decisions. In a previous study, using large BC cohorts and artificial neural network techniques, DNA replication and sister chromatid cohesion 1 (DSCC1) was found to be one of the principal genes in invasive BC samples. To date, no studies have addressed the prognostic significance of DSCC1 in invasive BC and its association with aggressive tumor behavior. This research aimed to address this gap. Materials and Methods: The association of clinicopathological features and patient outcomes with DSCC1 expression at the mRNA level was assessed using the Molecular Taxonomy Breast Cancer International Consortium (METABRIC; n = 1980) and The Cancer Genome Atlas (TCGA; n = 854) cohorts. DSCC1 was also evaluated at the protein level using immunohistochemistry on samples from invasive BC patients (n = 100) presenting to King Abdul Aziz Specialist Hospital in Saudi Arabia. The association of clinicopathological parameters (including patient age, tumor grade, tumor size, and patient outcome) with protein level was also evaluated. Results: In both METABRIC and TCGA cohorts, high expression of DSCC1 was significantly associated with high histological grade, large tumor size, lymphovascular invasion positivity, and hormone receptor negativity (all p < 0.001). A high DSCC1 mRNA level was associated with poor outcomes (p < 0.001 for METABRIC, p = 0.23 for TCGA). At the protein level, high DSCC1 expression was associated with high histological grade (p = 0.001), lymph node presence (p = 0.008), hormone receptor negativity (p = 0.005), high Ki67 expression (p = 0.036), and shorter survival (p = 0.008). Conclusions: This study confirmed the prognostic significance of DSCC1 in invasive BC patients. DSCC1 could be a therapeutic target in BC cases with poor outcomes.