A large number RNAs are enriched and stable in extracellular vesicles (EVs), and they can reflect their tissue origins and are suitable as liquid biopsy markers for cancer diagnosis and treatment efficacy prediction. In this study, we used extracellular vesicle long RNA (exLR) sequencing to characterize the plasma-derived exLRs from 112 breast cancer patients, 19 benign patients and 41 healthy participants. The different exLRs profiling was found between the breast cancer and non-cancer groups. Thus, we constructed a breast cancer diagnostic signature which showed high accuracy with an area under the curve (AUC) of 0.960 in the training cohort and 0.900 in the validation cohort. The signature was able to identify early stage BC (I/II) with an AUC of 0.940. Integrating the signature with breast imaging could increase the diagnosis accuracy for breast cancer patients. Moreover, we enrolled 58 patients who received neoadjuvant treatment and identified an exLR (exMSMO1), which could distinguish pathological complete response (pCR) patients from non-pCR with an AUC of 0.790. Silencing MSMO1 could significantly enhance the sensitivity of MDA-MB-231 cells to paclitaxel and doxorubicin through modulating mTORC1 signaling pathway. This study demonstrated the value of exLR profiling to provide potential biomarkers for early detection and treatment efficacy prediction of breast cancer.

The maintenance of bone homeostasis includes both bone resorption by osteoclasts and bone formation by osteoblasts. These two processes are in dynamic balance to maintain a constant amount of bone for accomplishing its critical functions in daily life. Multiple cell type communications are involved in these two complex and continuous processes. In recent decades, an increasing number of studies have shown that osteogenic and osteoclastic extracellular vesicles play crucial roles in regulating bone homeostasis through paracrine, autosecretory and endocrine signaling. Elucidating the functional roles of extracellular vesicles in the maintenance of bone homeostasis may contribute to the design of new strategies for bone regeneration. Hence, we review the recent understandings of the classification, production process, extraction methods, structure, contents, functions and applications of extracellular vesicles in bone homeostasis. We highlight the contents of various bone-derived extracellular vesicles and their interactions with different cells in the bone microenvironment during bone homeostasis. We also summarize the recent advances in EV-loaded biomaterial scaffolds for bone regeneration and repair.

Context.— Whether androgen receptor (AR) expression can predict prognosis in breast cancer is under debate. Objective.— To analyze, retrospectively, the prognostic and treatment predictive ability of AR status in breast cancer. Design.— A total of 5765 patients diagnosed with primary invasive breast cancer without distant metastasis in the adjuvant setting were analyzed. The propensity score matching method was used to develop a new cohort of 3978 patients (1989 patients each) in which important prognostic factors were balanced. Results.— Positive AR expression is an independent prognostic factor for disease-free survival and overall survival. Estrogen receptor (ER)+ and progesterone receptor (PR)+ AR+ breast cancer patients were associated with the longest survival, whereas ER−PR−AR− breast cancer patients were associated with the shortest survival. The ER/PR/AR combinations could not predict the treatment effects for adjuvant trastuzumab but could be used for adjuvant chemotherapy and endocrine therapy selection. The worst survival was found in ER+PR−AR− patients receiving toremifene, ER+PR−AR+ patients receiving exemestane, ER+PR+AR− patients receiving anthracycline, and ER−PR−AR+ patients receiving taxanes. ER+PR−AR−, ER−PR−AR+, and ER−PR−AR− patients were associated with the worst survival among those who received radiotherapy and anthracycline plus taxanes. Conclusions.— AR in combination with ER and PR could predict the prognosis and treatment effects of chemotherapy, endocrine therapy, and radiotherapy in the adjuvant setting.