Abstract
BackgroundLimited 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.MethodsThe 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.ResultsOur 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.ConclusionsOur 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.
Highlights
In the past decade, tumor-derived exosomes (50–150 nm) have been heavily studied in cancer development, metastasis, and drug resistance
annexin A2 (AnxA2) is expressed in exosomes isolated from serum samples of breast cancer patients We previously showed that AnxA2 is present in exosomes derived from the breast cancer cells [21]
Western blot analysis revealed that the serum exosomes were positive for the expression of exosomal protein markers CD9, TSG101, and flotillin-1 while calnexin, an endoplasmic reticulum marker not expressed in exosomes, is negative (Fig. 1b)
Summary
Tumor-derived exosomes (50–150 nm) have been heavily studied in cancer development, metastasis, and drug resistance. Tumor-derived exosomes are secreted into the bloodstream and are known to manipulate the metastatic cascade through angiogenesis, signal transduction, chemo-resistance, genetic intercellular exchange, and pre-metastatic-niche formation [4,5,6,7,8,9]. The investigation of tumor exosomes as a diagnostic or prognostic marker may offer new opportunities for a minimally invasive procedure that would adequately prognosticate and diagnose a disease progression in patients. Our previous studies have demonstrated annexin A2 (AnxA2) association with exosomes which promotes angiogenesis and metastasis. Our goal was to examine the expression and function of exosomal-annexin A2 (exo-AnxA2) derived from the serum samples of breast cancer patients
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