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

Objective: 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. Methods: 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. Results: 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, p p = 0.002), pT stage (T stage 2–4 vs. T stage 1: OR = 1.52, 95% CI = 1.07–2.17, p = 0.019), molecular human epidermal growth factor receptor 2 (HER2) status (positive vs. negative: OR = 1.61, 95% CI = 1.21–2.14, p = 0.001), epidermal growth factor receptor (EGFR) status (positive vs. negative: OR = 2.21, 95% CI = 1.13–4.33, p = 0.021), and worse disease-free survival (DFS) (HR = 2.66, 95% CI = 1.20–5.91, p = 0.016) of breast cancer. Conclusions: SOX2 expression is correlated with breast cancer progression, HER2 status, and EGFR status, and may be an independent prognostic marker for predicting poor DFS.研究目的：转录因子SOX2（sex-determining region Y-box 2）在干细胞状态的维持中发挥关键作用。然而，目前关于SOX2在乳腺癌中作用的相关研究证据尚存矛盾。本研究开展此项荟萃分析，以明确SOX2表达与乳腺癌临床及分子特征的关联，及其对乳腺癌的预后价值。 研究方法：通过电子数据库检索所有相关文献。计算合并比值比（odds ratios，OR）或风险比（hazard ratios，HR，多因素Cox生存分析）及其95%置信区间（confidence intervals，CI）。 研究结果：最终共纳入18项研究，涉及3080例乳腺癌患者。分析显示，SOX2蛋白表达与患者年龄、绝经状态、淋巴结转移、脉管侵袭、雌激素受体分子状态、孕激素受体分子状态、三阴性亚型状态及乳腺癌总生存率均无显著相关性，但与高级别肿瘤分级（3级 vs 1~2级：OR=2.74，95%CI=1.85~4.06，p=0.002）、pT分期（T分期2~4期 vs T1期：OR=1.52，95%CI=1.07~2.17，p=0.019）、人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）分子状态（阳性 vs 阴性：OR=1.61，95%CI=1.21~2.14，p=0.001）、表皮生长因子受体（epidermal growth factor receptor，EGFR）分子状态（阳性 vs 阴性：OR=2.21，95%CI=1.13~4.33，p=0.021）以及较差的无病生存期（disease-free survival，DFS）（HR=2.66，95%CI=1.20~5.91，p=0.016）密切相关。 研究结论：SOX2表达与乳腺癌进展、HER2状态及EGFR状态显著相关，可作为预测乳腺癌不良无病生存期的独立预后标志物。