Exosome‑encapsulated microRNA‑223‑3p as a minimally invasive biomarker for the early detection of invasive breast cancer

Abstract

Patients diagnosed preoperatively with ductal carcinoma (DCIS) breast cancer have the potential to develop invasive ductal carcinoma (IDC). The present study investigated the usefulness of exosome-encapsulated microRNA-223-3p (miR-223-3p) as a biomarker for detecting IDC in patients initially diagnosed with DCIS by biopsy. The potential association between miR-223-3p and clinicopathological characteristics was examined in patients with breast cancer. Exosomes of 185 patients with breast cancer were separated from plasma by ultracentrifugation. Initially a microRNA (miRNA) microarray was examined to reveal the invasion specific miRNAs using exosomes collected from 6 patients with breast cancer, including 3 DCIS patients, 3 IDC patients and 3 healthy controls. In the miR microarray analysis the miR-223-3p levels of IDC patients demonstrated the highest fold-change compared with those in the DCIS patients and healthy controls. The potential of miR-223-3p for cell proliferation and cell invasion were examined using MCF7 cells transfected with the miR-223-3p gene. MCF7 cells transfected with the miR-223-3p gene significantly promoted cell proliferation and cell invasive ability (P<0.05). The plasma exosomal miR-223-3p levels of the other 179 patients with breast cancer and 20 healthy controls were measured using TaqMan miR assays. The exosomal miR-223-3p levels of the patients with breast cancer were significantly increased compared with the healthy controls (P<0.01). A statistically significant association was observed between the exosomal miR-223-3p levels and histological type, pT stage, pN stage, pathological stage, lymphatic invasion and nuclear grade (P<0.05). The exosomal miR-223-3p levels of IDC patients (stage I) and upstaged IDC patients (stage I) were significantly higher compared with the DCIS patients (P<0.05). These results suggest that exosomal miR-223-3p may be a useful preoperative biomarker to identify the invasive lesions of DCIS patients diagnosed by biopsy. In addition, plasma exosome-encapsulated miR-223-3p level was significantly associated with the malignancy of breast cancer.

Identification of a six‐miRNA panel in serum benefiting pancreatic cancer diagnosis

“…Interestingly, miR‐192‐5p, miR‐19a‐3p, and miR‐19b‐3p were still upregulated in exosomes as in serum and tissues. Though exosome‐encapsulated miR‐223‐3p was once reported to be noninvasive biomarker for breast cancer, no significant statistical difference was observed for PC in this study . To date, there were still few reports being published on the exosomes miRNAs characteristics of PC patients.…”

Exosomal microRNA‑210 is a potentially non‑invasive biomarker for the diagnosis and prognosis of glioma

“…Levels of serum exo-miR-1290 and exo-miR-375 are associated with castration resistance in prostate cancer (39). miR-223-3p encapsulated by exosomes has been identified as an important biomarker for the early detection of invasive breast cancer (40). Exo-miR-423-5p has been reported as a minimally invasive biomarker in the diagnosis of gastric cancer, and can promote tumor growth and metastasis by targeting SUFU negative regulator of hedgehog signaling (41).…”

Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer

“…There have been a number of initial studies investigating circulating EV-miRNAs as biomarkers of breast cancer in recent years [5,[16][17][18][19][20][21]. Although limited by control sample size, one study reported elevation of miRNA-101 and miRNA-372 in serum-derived EVs of patients with breast cancer (n = 50) compared to healthy controls (n = 12) [5].…”