BACKGROUND Limited information is available on biomarker(s) for triple-negative breast cancer (TNBC) that can address the higher incidence and aggressiveness of TNBC in African-American (AA) women. Our previous studies have demonstrated annexin A2 (AnxA2) association with exosomes which promotes angiogenesis and metastasis. Therefore, our goal was to examine the expression and function of exosomal-annexin A2 (exo-AnxA2) derived from the serum samples of breast cancer patients. METHODS The expression of serum exo-AnxA2 and its association with clinicopathological features of the breast cancer patients were determined. The role of serum exo-AnxA2 to promote angiogenesis was determined by an in vivo Matrigel plug assay. RESULTS Our results show that the expression of serum exo-AnxA2 in breast cancer patients (n = 169; 83.33 ± 2.040 ng/mL, P < 0.0001) is high compared to non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). High expression of exo-AnxA2 levels in breast cancer was significantly associated with tumor grade (P < 0.0001), poor overall survival (hazard ratio (HR) 2.802; 95% confidence intervals (CI) = 1.030-7.620; P = 0.0353), and poor disease-free survival (HR 7.934; 95% CI = 1.778-35.398; P = 0.0301). The expression of serum exo-AnxA2 levels was significantly elevated in TNBC (n = 68; 109.1 ± 2.905 ng/mL; P < 0.0001) in comparison to ER+ (n = 50; 57.35 ± 1.545 ng/mL), HER2+ (n = 59; 78.25 ± 1.146 ng/mL), and non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). Exo-AnxA2 showed diagnostic values with a maximum AUC as 1.000 for TNBC, 0.8304 for ER+, and 0.9958 for HER2+ compared to non-cancer females. The expression of serum exo-AnxA2 was significantly elevated in AA women with TNBC (n = 29; 118.9 ± 4.086 ng/mL, P < 0.0001) in comparison to Caucasian-American TNBC (n = 27; 97.60 ± 3.298 ng/mL) patients. Our in vivo results suggest a role of serum exo-AnxA2 in angiogenesis and its association with aggressiveness of TNBC in AA women. CONCLUSIONS Our results demonstrated that the expression of serum exo-AnxA2 is high in AA women with TNBC and promotes angiogenesis. These findings suggest that exo-AnxA2 holds promise as a potential prognosticator of TNBC and may lead to an effective therapeutic option.

中文翻译：

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血清外泌体-膜联蛋白 A2 与非裔美国人三阴性乳腺癌相关并促进血管生成。

背景 关于三阴性乳腺癌 (TNBC) 的生物标志物的可用信息有限，这些生物标志物可以解决非裔美国人 (AA) 女性中 TNBC 的较高发病率和侵袭性。我们之前的研究已经证明膜联蛋白 A2 (AnxA2) 与促进血管生成和转移的外泌体相关。因此，我们的目标是检查来自乳腺癌患者血清样本的外泌体-膜联蛋白 A2 (exo-AnxA2) 的表达和功能。方法检测乳腺癌患者血清exo-AnxA2的表达及其与临床病理特征的关系。血清 exo-AnxA2 促进血管生成的作用通过体内 Matrigel plug 试验确定。结果 我们的结果显示，乳腺癌患者血清 exo-AnxA2 的表达 (n = 169; 83.33 ± 2.040 ng/mL, P < 0. 0001) 高于非癌症女性 (n = 68; 34.21 ± 2.238 ng/mL)。exo-AnxA2 水平在乳腺癌中的高表达与肿瘤分级 (P < 0.0001)、较差的总体生存率 (风险比 (HR) 2.802；95% 置信区间 (CI) = 1.030-7.620；P = 0.0353)、无病生存率低（HR 7.934；95% CI = 1.778-35.398；P = 0.0301）。与 ER+ (n = 50; 57.35 ± 1.545 ng/mL)、HER2+ (n = 59；78.25 ± 1.146 纳克/毫升）和非癌症女性（n = 68；34.21 ± 2.238 纳克/毫升）。与非癌症女性相比，Exo-AnxA2 的诊断价值最大 AUC 为 TNBC 1.000、ER+ 0.8304 和 HER2+ 0.9958。与高加索裔美国人 TNBC (n = 27; 97.60 ± 3.298 ng/mL) 相比，患有 TNBC 的 AA 女性的血清外切-AnxA2 表达显着升高 (n = 29; 118.9 ± 4.086 ng/mL, P < 0.0001)患者。我们的体内结果表明血清 exo-AnxA2 在血管生成中的作用及其与 AA 女性 TNBC 侵袭性的关联。结论 我们的结果表明，患有 TNBC 的 AA 女性血清外切 AnxA2 的表达高，并促进血管生成。这些发现表明，exo-AnxA2 有望成为 TNBC 的潜在预后因子，并可能带来有效的治疗选择。我们的体内结果表明血清 exo-AnxA2 在血管生成中的作用及其与 AA 女性 TNBC 侵袭性的关联。结论 我们的结果表明，患有 TNBC 的 AA 女性血清外切 AnxA2 的表达高，并促进血管生成。这些发现表明，exo-AnxA2 有望成为 TNBC 的潜在预后因子，并可能带来有效的治疗选择。我们的体内结果表明血清 exo-AnxA2 在血管生成中的作用及其与 AA 女性 TNBC 侵袭性的关联。结论 我们的结果表明，患有 TNBC 的 AA 女性血清外切 AnxA2 的表达高，并促进血管生成。这些发现表明，exo-AnxA2 有望成为 TNBC 的潜在预后因子，并可能带来有效的治疗选择。