Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Placental Delta-Like 1 Gene DNA Methylation Levels Are Related to Mothers' Blood Glucose Concentration.

PURPOSE: We aim to identify the methylation status of delta-like 1 (DLK1) in the placenta and the correlation between DLK1 methylation and maternal serum glucose level and fetal birth weight. METHODS: We analyzed the gene expression of DLK1 gene in both maternal and fetal sides of the placenta in a GDM group (n = 15) and a control group (n = 15) using real-time polymerase chain reaction. With MethylTargetTM technique, we detected the methylation status of DLK1 promotor in the placenta. Furthermore, Pearson's correlation was used to confirm the association of methylation alteration of DLK1 promoter and maternal 2 h OGTT glucose level and fetal birth weight. RESULTS: In our study, we found that DLK1 expression in both maternal and fetal sides of the placenta decreased significantly in GDM group compared with control group, and it was caused by hypermethylation of DLK1 promoter region. Additionally, the methylation status of DLK1 gene in the maternal side of the placenta highly correlated with maternal 2 h OGTT glucose level (coefficient = 0.7968, P < 0.0001), while the methylation status in the fetal side of the placenta was closely related to fetal birth weight (coefficient = 0.6233, P < 0.0001). CONCLUSIONS: Our results demonstrated that altered expression of DLK1 was caused by the hypermethylation of DLK1 promoter region in the placenta, and intrauterine exposure to GDM has long-lasting effects on the epigenome of the offspring.

Type 2 Cesarean Scar Pregnancy Successfully Treated via Hysteroscopy-Assisted Laparoscopy.

STUDY OBJECTIVE: To evaluate the efficacy of hysteroscopy-assisted laparoscopy as a treatment strategy for type 2 cesarean scar pregnancy at gestational age >8 weeks. DESIGN: Retrospective case series (Canadian Task Force classification II-3). SETTING: A tertiary hospital. PATIENTS: Eight women with type 2 cesarean scar pregnancy at a gestational age >8 weeks. INTERVENTIONS: All patients underwent hysteroscopy-assisted laparoscopic resection and isthmus repair of cesarean scar pregnancy. MEASUREMENTS AND MAIN RESULTS: All patients underwent removal of the cesarean scar pregnancy and complete repair of the uterine scar defect. The median operative time was 123.0 minutes (range, 100-168 minutes), median blood loss was 65.0 mL (range, 20-100 mL), and median length of hospital stay was 9.1 days (range, 8-12 days). There were no adverse reactions. The mean time to serum ß-human chorionic gonadotropin (ß-HCG) resolution was 22.9 days (range, 14-30 days), and menstruation resumed after 9 to 15 days with serum ß-HCG returning to nondetectable levels. There was no recurrence of cesarean scar pregnancy at long-term follow-up. CONCLUSION: Hysteroscopy-assisted laparoscopy may be an effective treatment for patients with type 2 cesarean scar pregnancy at gestational age >8 weeks.

Establishing a Nomogram for Stage IA-IIB Cervical Cancer Patients after Complete Resection.

BACKGROUND: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. MATERIALS AND METHODS: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. RESULTS: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. CONCLUSIONS: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.

Methotrexate induces apoptosis of human choriocarcinoma cell line JAR via a mitochondrial pathway.

OBJECTIVE: To investigate methotrexate (MTX)-induced apoptosis and the involved pathways in human choriocarcinoma cells. STUDY DESIGN: MTX-induced apoptosis of human choriocarcinoma cell line JAR was examined using a PI/Annexin V stain with flow cytometer (FCM). Mitochondrial apoptosis was detected by fluorescence microscopy, and analyzed by FCM using a MitoCapture mitochondrial apoptosis detection kit. The activities of caspase-8 and caspase-9 were quantified by microtiter plate reader at 405 nm using FLICE/Caspase-8 colorimetric assay kit and Caspase-9/Mch6 colorimetric assay kit. The changes in Bax and Bcl-2 expression were detected during apoptosis using immunocytochemistry and Western blot analysis. RESULTS: JAR cells underwent apoptosis after exposure to 0.1-2.5 microg/ml MTX for 48 h. Decreased mitochondrial membrane potential was observed both by fluorescence microscopy and FCM. The activation of caspase-9 was increased 4.35+/-0.76-fold in MTX-incubated JAR, while there was no obvious change in the activation of caspase-8. When JAR cells underwent apoptosis, the expression of Bcl-2 was decreased and the expression of Bax was increased; both were detected by immunocytochemistry assay. CONCLUSION: Methotrexate in lower concentrations induces apoptosis of human choriocarcinoma cells via mitochondrial-initiated pathways, including reduction of mitochondrial membrane potential, activation of caspase-9, and up-regulation of Bax/Bcl-2 expression.