Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.

Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Radiotherapy is one of the main strategies for GC treatment, while development of radioresistance limits the effectiveness. microRNA-203 (miR-203) has been reported to participate in progression of GC, whereas its interaction with radiosensitivity of GC and the related mechanism remain largely unclear. Methods: The expressions of miR-203 and zinc finger E-box binding homeobox 1 (ZEB1) were measured in GC tissues and cells by quantitative real-time polymerase chain reaction or western blot. Survival fraction, cell viability and apoptosis were measured in GC cells after treatment of radiation by colony formation, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay or flow cytometry, respectively. Tumor volume and weight were detected in murine xenograft model after radiation treatment. The interaction between miR-203 and ZEB1 was explored by bioinformatics analysis and luciferase activity assay. Results: miR-203 expression was down-regulated and ZEB1 mRNA level was up-regulated in GC. The expression of miR-203 was associated with radiosensitivity of GC cells. Moreover, overexpression of miR-203 decreased survival fraction, cell viability and tumor growth but promoted cell apoptosis in radiation-treated GC cells. However, knockdown of miR-203 played an opposite effect. ZEB1 was validated as a target of miR-203, and it was involved in miR-203-mediated radiosensitivity of GC cells in vitro and in vivo. Conclusion: miR-203 promoted radiosensitivity of GC cells by targeting ZEB1, indicating miR-203 as a promising radiosensitizer for GC treatment.

Medical therapeutic options remain quite limited for uterine fibroids treatment. Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have anti-tumoral effects on multiple cancer types, however, little is known about their effects on uterine fibroids. Initially, we conducted a retrospective study of 120 patients with uterine fibroids and hyperlipidemia from the Second Affiliated Hospital of Wenzhou Medical University. Then, we evaluated the effect of atorvastatin on proliferation and apoptosis both in immortalized uterine fibroids cells and primary uterine fibroids cells. Furthermore, the molecular mechanism by which atorvastatin suppressed uterine fibroids cell growth was explored. Our results showed that atorvastatin use for 1 or 2 years significantly suppressed growth of uterine fibroids. Atorvastatin inhibited the proliferation of immortalized and primary uterine fibroids cells in a dose and time-dependent manner and stimulated apoptosis of uterine fibroids cells by inducing caspase-3 activation, up-regulating Bim and down-regulating Bcl-2. Additionally, atorvastatin treatment suppressed phosphorylation of ERK1/2 and JNK. Furthermore, GGPP, a downstream lipid isoprenoid intermediate, significantly rescued the effect of atorvastatin. These results suggest that atorvastatin exerts anti-tumoral effects on uterine fibroids through inhibition of cell proliferation and induction of apoptosis in HMG-CoA-dependent pathway. Our results provide the first clinical and preclinical data on the use of atorvastatin as a promising nonsurgical treatment option for uterine fibroids.

Background: The basal luteinizing hormone (LH) and the prior LH to follicle-stimulating hormone (FSH) ratio (LH/FSH) in polycystic ovarian syndrome (PCOS) are generally higher than those in non-PCOS patients and the general population. The potential negative effects of elevated LH on human reproductive function are highly controversial, as are the effects of down-regulation of LH on reproductive function. The purpose of this study was to evaluate the effect of the basal LH/FSH ratio on the live birth rate of PCOS patients undergoing in vitro fertilization (IVF) cycles. Methods: A retrospective analysis was conducted on 698 patients with polycystic ovary syndrome undergoing IVF treatments with a mild stimulation protocol (n = 95) and a gonadotropin-releasing hormone (GnRH) agonist protocol (n = 603). The basal LH/FSH ratio of 2 was used as the cut-off value for further subgroup analysis. The demographic properties, controlled ovarian hyperstimulation (COH) processes, and clinical pregnancy outcomes were compared between groups under each ovulation stimulation protocol. Results: The live birth rate for patients with a LH/FSH ratio ≥ 2 group (56.38%, n = 149) was not statistically different from that of the ones with a ratio < 2 (53.74%, n = 454) in the GnRH agonist protocol (P = 0.576). Correspondingly, the live birth rate for the LH/FSH ratio ≥ 2 group (43.48%, n = 23) also showed no statistical difference from the ratio < 2 group (48.61%, n = 72) in the mild stimulation protocol (P = 0.668). Additionally, LH/FSH ratios had no significant effect on the live birth rate after adjusting for confounders both in the GnRH agonist protocol (adjusted OR: 1.111; 95% CI [0.467–2.642], P = 0.812) and in the mild stimulation protocol (adjusted OR: 4.057; 95% CI [0.431–38.195], P = 0.221). Furthermore, there was no significant difference in the live birth rate between different ovulation stimulation protocols in PCOS patients with the LH/FSH ratio ≥ 2. Conclusions: The live birth rate in IVF outcomes was not affected by an elevated basal LH/FSH ratio in patients with polycystic ovary syndrome. The choice of the GnRH agonist protocol or mild stimulation protocol for ovulation stimulation does not affect the final clinical outcomes either for PCOS patients with a basal LH/FSH ratio ≥ 2.