OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer associated with worse survival outcomes in African American (AA) patients. This study evaluated tumor miRNA expression by race, clinical and tumor characteristics, and survival outcomes.
METHODS: FFPE tumor tissue from hysterectomy specimens was identified for 29 AA cases. Case matching was performed by computer-based random assignment in a 1:1 ratio with Caucasian controls based on age, stage and histologic subtype (pure vs. mixed). RNA was extracted from 77 specimens (54 tumors and 23 matched normal endometrium). MicroRNA array profiling was performed by microRNA Hi-Power Labeling (Hy3/Hy5) and hybridization to miRCURY LNA microRNA Array 7th Gen.
RESULTS: Clinical and treatment characteristics were similar for cases and controls, although use of adjuvant radiation was less common in African Americans (p = 0.03). Of 968 miRNAs analyzed, 649 were differentially expressed in normal endometrium vs. tumor. When compared by race, histologic subtype, stage or presence of LVI, no differentially expressed miRNAs were identified. In patients with disease recurrence at 3 years, the three most upregulated miRNAs were miR-1, miR-21-5p and miR-223. Of these, increased miR-223 expression (>median) was associated with worse OS (p = 0.0496) in an independent dataset (TCGA dataset) comprising of 140 patients with USC (mixed or pure serous). After adjusting for age, ethnicity and BMI, upregulation of miR-223 remained risk factor for death (adjusted HR 2.87, 95% CI 1.00-8.27).
CONCLUSIONS: MiRNA profiling did not identify biological differences between AA and Caucasian patients with USC. Upregulation of miR-223 may be a prognostic factor in USC.

Osteosarcoma (OS) is a malignant neoplasia in bone, characterized with main occurrence in teenagers. Calycosin (CC), a bioactive compound, is found to play potent pharmacological effects against cancer. Our previous study indicates CC-exerted benefits for anti-OS effect. However, further molecular mechanism behind this action needs to be investigated. In this study, human OS samples and clinical data were collected and used for further test and analysis. In addition, human osteosarcoma cell line (143B) and tumor-xenograft nude mice were used to evaluate antineoplastic activities of CC through a series of biochemical methods and immunoassays, respectively. Compared with non-OS controls, human OS samples showed increased levels of neoplastic microRNA-223 (miR-223), and elevated expressions of NF-κBp65, IκBα proteins in tumor cells. In cell culture study, CC-treated 143B cells showed reduced cell growth, increased lactic dehydrogenase (LD) content, and downregulated cellular miR-223 level. Immunolabeled cells of proliferating cell nuclear antigen, B-cell lymphoma 2 (Bcl-2), poly(ADP-ribose) polymerase (PARP) in CC treatments were decreased dose-dependently, while caspase-3 positive cells were elevated. Further, protein expressions of NF-κBp65, IκBα in CC-treated cells were downregulated. In addition, tumor-xenograft nude mice followed by CC treatments exhibited reductions of tumor mass, miR-223 levels, and Bcl-2, PARP-positive cells, as well as downregulations of NF-κBp65, IκBα protein expressions in OS samples. Taken together, these experimental findings reveal that CC exhibits potential pharmacological activities against OS through inducing apoptosis and inhibiting miR-223-IκBα signaling pathway in neoplastic cells.