Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis.

Abstract

PurposeThere is an urgent need for new biomarkers for the diagnosis of breast cancer. Exosomes can communicate with cells through transport molecules, including long-chain noncoding RNA (lncRNA), which is considered as a promising noninvasive biomarker. Here, we aimed to determine the potential of long noncoding RNA (lncRNA) H19 in the circulating exosomes for the diagnosis of breast cancer (BC).Materials and MethodsWe measured the levels of lncRNA H19 in serum-derived exosomes from patients with breast cancer (BC) or benign breast disease (BBD) and healthy subjects, using quantitative real-time PCR. H19 levels were also measured for pre-operative and post-operative patients. Receiver operating characteristic curve was constructed, and the area under the curve (AUC) was calculated to determine the applicability of exosomal H19 levels as biomarkers in BC. The relationship between H19 relative expression and clinical features of BC patients was also analyzed.ResultsExosomal H19 expression levels were upregulated in patients with BC compared to that in patients with BBD and healthy controls (BC vs BBD, P < 0.001; BC vs healthy subjects, P < 0.001). The median serum exosomal H19 levels were significantly lower in post-operative than that in the pre-operative patients (P < 0.001). The AUC for exosomal H19 analysis was 0.870 (95% CI: 0.774–0.966) with a sensitivity of 87.0% and specificity of 70.6%, which was higher than the AUCs for CA15-3 and CEA, ie, 0.822 and 0.811, respectively. Moreover, exosomal H19 expression levels were associated with lymph node metastasis (P = 0.039), distant metastasis (P = 0.008), TNM stages (P = 0.022), ER (P=0.009), PR (P = 0.018), and Her-2 (P = 0.021).ConclusionOur results indicated that serum exosomal H19 acts as a novel biomarker for the diagnosis of BC.