Congenital uterine anomalies (CUA) may influence reproductive performance, resulting in adverse pregnancy associated complications. This study aimed to assess the association of CUA subtypes with reproductive, obstetric, and perinatal outcomes. We performed a systematic search of the MEDLINE, EMBASE, and Cochrane libraries for studies comparing pregnancy outcomes between women with CUA and those with a normal uterus. The random effects model was used to estimate the odds ratios (ORs) with a 95% confidence interval (CI). Women with CUA had a lower rate of live births (OR 0.47; 95% CI 0.33–0.69), and a higher rate of first trimester miscarriage (OR, 1.79; 95% CI 1.34–2.4), second trimester miscarriage (OR 2.92; 95% CI 1.35–6.32), preterm birth (OR 2.98; 95% CI 2.43–3.65), malpresentation (OR 9.1; 95% CI 5.88–14.08), cesarean section (OR 2.87; 95% CI 1.56–5.26), and placental abruption (OR 3.12; 95% CI 1.58–6.18). Women with canalization defects appear to have the poorest reproductive performance during early pregnancy. However, unification defects were associated with obstetric and neonatal outcomes throughout the course of pregnancy. It may be beneficial for clinicians to advise on potential complications that may be increased depending on the type and severity of CUA.
The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.922 indicated good diagnostic accuracy for Nectin-4 expression in EC. Furthermore, Nectin-4 expression was associated with DNA mismatch repair (MMR) protein deficiency. Notably, the high Nectin-4 expression group of patients with MSH2/6-deficient EC had shorter progression-free survival than that of the low Nectin-4 expression group. The number of lymphovascular space invasion-positive patients in groups with MMR deficiency and high Nectin-4 expression was also increased compared with that in the low Nectin-4 expression group. Bioinformatics analysis revealed that alteration in Nectin-4 and MMR genes is associated with Nectin-4 expression in EC. To the best of our knowledge, this is the first study to show that Nectin-4 expression may be a potential biomarker for EC diagnosis and that high Nectin-4 expression in MMR-deficient patients with EC can predict short progression-free survival, thus providing clues to identify patients for adjuvant therapy.
Patient-derived xenografts (PDXs) are important in vivo models for the development of precision medicine. However, challenges exist regarding genetic alterations and relapse after primary treatment. Thus, PDX models are required as a new approach for preclinical and clinical studies. We established PDX models of gynecologic cancers and analyzed their clinical information. We subcutaneously transplanted 207 tumor tissues from patients with gynecologic cancer into nude mice from 2014 to 2019. The successful engraftment rate of ovarian, cervical, and uterine cancer was 47%, 64%, and 56%, respectively. The subsequent passages (P2 and P3) showed higher success and faster growth rates than the first passage (P1). Using gynecologic cancer PDX models, the tumor grade is a common clinical factor affecting PDX establishment. We found that the PDX success rate correlated with the patient’s prognosis, and also that ovarian cancer patients with a poor prognosis had a faster PDX growth rate (p < 0.0001). Next, the gene sets associated with inflammation and immune responses were shown in high-ranking successful PDX engraftment through gene set enrichment analysis and RNA sequencing. Up-regulated genes in successful engraftment were found to correlate with ovarian clear cell cancer patient outcomes via Gene Expression Omnibus dataset analysis.