Abstract 147P
Background
Breast cancer is the most common malignant tumor in women. Axillary lymph node (ALN) status is an independent risk factor of prognosis and correlates with distant metastasis. However, the relation between tumor-derived exosomal miRNAs and the lymph node metastases in breast cancer is still unclear. Meanwhile, biomarkers based on serum exosome for clinical applications were underdeveloped.
Methods
In this study, RNA sequencing (RNAseq) analysis at high depth sequencing was used aiming to characterize the miRNA expression landscape in the serum exosomes from breast cancer patients. The candidate miRNAs responsible for breast cancer LNM were generated by comparing the miRNA expression difference between patients with or without LNM. Additionally, the candidate miRNAs were verified in multiple public datasets. Furthermore, in silico and experimental studies were performed to identify potentially relevant target genes of the candidate miRNA and the underline mechanism of the LNM in the breast cancer.
Results
Exosomal hsa-miR-363-5p was found to be significantly downregulated in breast cancers with ALN metastasis (P=0.019). In silico analysis verified that high miR-363-5p level correlates with negative lymph node (P=0.0022) and better patient survival (P=0.0075). External data revealed significant diagnostic value of exosomal miR-363-5p in predicting lymph node metastasis (AUC=0.621-0.733). Functional experiments discovered that miR-363-5p acts by inhibiting migration ability of breast cancer cell. We identified Platelet Derived Growth Factor Subunit B (PDGFB) as a direct downstream target of miR-363-5p.
Conclusions
the miR-363-5p deficiency promoted metastasis via facilitating PDGFB expression, leading to overactivity of PDGF signaling in cancer cells. Exosomal miR-363-5p may serve as a marker for ALN metastasis diagnosis in a non-invasive manner.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
National Cancer Center /National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Funding
Chinese Academy of Medical Sciences.
Disclosure
All authors have declared no conflicts of interest.