ABSTRACT
To investigate the source of serum exosomal HOTAIR, to uncover the diagnostic and prognostic values of serum exosomalHOTAIR, and to discern the expression of serum exosomal HOTAIR between neoadjuvant chemotherapy and response totamoxifen therapy. Samples were collected from the Third Affiliated Hospital of Kunming Medical University, TumorHospital of Yunnan. Exosomes were isolated from serum, cell culture medium and tumor tissues. We used transmissionelectron microscopy and western immunoblotting assay to characterize exosomes, and real-time PCR (qPCR) to assessHOTAIR expression. Neoadjuvant chemotherapy and tamoxifen therapy were carried out according to establishedguidelines. Breast cancer patients expressed higher serum exosomal HOTAIR than did healthy individuals (P \ 0.001).Serum exosomal HOTAIR levels 3 months after surgery were markedly decreased compared with levels before surgery(P \0.001), and the expression level of exosomal HOTAIR in cell culture medium increased with time in both breastcancer cell lines (72 h [48 h[ 24 h, 48 h vs 24 h [P \ 0.05]; 72 h vs 24 h [P \ 0.01]). Expression of serum exosomalHOTAIR in nude mice was notably greater than in the mock control group (P \0.001). The results of the ROC analysisrevealed an AUC for serum exosomal HOTAIR of 0.9178 with a 95% CI of 0.8407–1.017 (P \0.01). The AUC for theCA15-3 cell line was 0.7378 (95% CI, 0.5585–0.9170; P = 0.03). High expression of exosomal HOTAIR led to a worsedisease-free survival (P = 0.0481) and overall survival (P = 0.0463). In the high-expression chemotherapy group, sixpatients achieved a partial response (PR) and eight demonstrated stable disease (SD) and nine patients achieved PR and twoSD in the low-expression group (P = 0.048). In the low-expression tamoxifen group, one patient had a recurrence of breastcancer and another 10 patients exhibited no recurrence, while six showed recurrence, and seven had none in the highexpression group (P = 0.035). We isolated exosomes successfully, and demonstrated that serum exosomal HOTAIRoriginated from primary breast cancer tissue. We conclude that serum exosomal HOTAIR exhibits the potential to be adiagnostic and prognostic biomarker. High expression of serum exosomal HOTAIR was also correlated with poorneoadjuvant chemotherapy and response to tamoxifen therapy.