The Clinical and Molecular Characteristics of Sex-Determining Region Y-Box 2 and its Prognostic Value in Breast Cancer: A Systematic Meta-Analysis

Abstract

<b><i>Objective:</i></b> Transcription factor SOX2 (sex-determining region Y-box 2) has a crucial role in the maintenance of the stem cell state. However, current evidence regarding the role of SOX2 in breast cancer is conflicting. We conducted this meta-analysis to clarify the association of SOX2 expression with clinical and molecular features and its prognostic effect on breast cancer. <b><i>Methods:</i></b> All relevant articles were searched using electronic databases. The pooled odds ratios (ORs) or hazard ratios (HRs: multivariate Cox survival analysis) with their 95% confidence intervals (CIs) were calculated. <b><i>Results:</i></b> A final total of 18 studies containing 3,080 patients with breast cancer were included. SOX2 protein expression was not related to age, menopausal status, lymph node metastasis, lymphovascular invasion, molecular estrogen receptor status, progesterone receptor status, triple-negative status, and the overall survival in breast cancer, but was closely associated with advanced tumor grade (grade 3 vs. grade 1–2: OR = 2.74, 95% CI = 1.85–4.06, <i>p</i> &#x3c; 0.001), clinical stage (stage 3–4 vs. stage 0–2: OR = 2.46, 95% CI = 1.37–4.40, <i>p</i> = 0.002), pT stage (T stage 2–4 vs. T stage 1: OR = 1.52, 95% CI = 1.07–2.17, <i>p</i> = 0.019), molecular human epidermal growth factor receptor 2 (HER2) status (positive vs. negative: OR = 1.61, 95% CI = 1.21–2.14, <i>p</i> = 0.001), epidermal growth factor receptor (EGFR) status (positive vs. negative: OR = 2.21, 95% CI = 1.13–4.33, <i>p</i> = 0.021), and worse disease-free survival (DFS) (HR = 2.66, 95% CI = 1.20–5.91, <i>p</i> = 0.016) of breast cancer. <b><i>Conclusions:</i></b> SOX2 expression is correlated with breast cancer progression, HER2 status, and EGFR status, and may be an independent prognostic marker for predicting poor DFS.