MicroRNA 421 induces the formation of high-invasive cell subsets of ovarian cancer from low-invasive cell subsets mediated by exosomes by activating the PI3K/AKT pathway.

Intratumoral heterogeneity (ITH) results in treatment failure in ovarian cancer (OC). Exosomes are related to the formation of a heterogeneous tumor microenvironment, and microRNAs play a crucial role in the progression of OC. Therefore, we aimed to explore the effect of exosomes and microRNA 421 (miR-421), which is mediated by exosomes, on ITH and the diagnosis of OC. Exosomes derived from A2780 cells with the highest (AHC) or lowest (ALC) invasive/migratory capacity cells (AHE/ALE) were extracted by differential centrifugation. We conducted a series of experiments to verify the role of AHE and miR-421 in promoting the transformation of low-invasive cells to high-invasive cells by regulating the PI3K/AKT pathway, and we also measured the levels of CA125 in serum exosomes. The results of assays showed that the AHE and miR-421, mediated by exosomes, significantly increased the malignancy of ALC cells by activating the PI3K/AKT pathway. The expression of miR-421 was significantly increased in the serum exosomes derived from high-grade serous ovarian cancer (HGSOC) patients. Our findings indicate that MiR-421, mediated by exosomes, could induce the transformation of highly invasive cell subpopulations from subpopulations of OC cells with low invasive potential by activating the PI3K/AKT signaling pathway.

Clinical Analysis and Prognostic Prediction Model for Patients with Uterine Leiomyosarcoma at FIGO Stage I.

Purpose: To reveal the clinical status and construct a predictive prognostic model for patients with uterine leiomyosarcoma (uLMS) at International Federation of Gynecology and Obstetrics (FIGO) stage I. Patients and Methods: The medical records of patients with stage I uLMS during the study period were retrospectively reviewed. Multiple imputation, Martingale residuals and restricted cubic spline were used for data processing. Univariate and multivariate analyses were used to determine independent prognostic factors. The Schoenfeld individual test was used to verify the proportional hazards (PH) assumption. The predictive ability of the nomogram was validated internally. Results: Ultimately, 102 patients were included. The median age at diagnosis was 51 years old. During the medium follow-up time of 68 months, 55 (53.9%) patients developed recurrence. The median recurrence interval was 32 months. The most common metastatic site was the lung (27 cases). Eventually, 38 (37.3%) patients died of uLMS. The 3-year and 5-year overall survival rates were 66.0% and 52.0%, respectively. Age at diagnosis >49 years, larger tumor size, MI>10/10HPF, presence of LVSI and Ki-67 labeling index (LI) >25% (P=0.0467, 0.0077, 0.0475, 0.0294, and 0.0427, respectively) were independent prognostic factors. The PH assumption remained inviolate. The concordance index was 0.847, the area under the time-dependent receiver operating characteristic curve surpassed 0.7, and the calibration curve showed gratifying consistency. Conclusion: Age at diagnosis, tumor size, MI, LVSI, and Ki-67 LI were identified as independent prognostic factors for stage I uLMS. This prognostic nomogram would provide personalized assessment with superior predictive performance.