Purpose Persistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion. Methods WNT1 and miR-34a expression levels were assessed in primary cervical lesions using immunohistochemistry and qRT-PCR, respectively. The cellular effects and the expression of its associated genes were examined in cervical SCC-derived Siha and Caski cells after siRNA-WNT1 (downregulation) or miR-34a mimic (upregulation) treatment. A cervical SCC xenograft mouse model was used to investigate the in vivo effects of miR-34a overexpression. HPV-16 E6/E7 expression was inhibited by gene promoter siRNA targeting, after which the levels of miR-34a and WNT1 were examined. Results WNT1 protein upregulation was found to be associated with a poor prognosis in cervical SCC patients. In vitro assays in Siha and Caski cells revealed that WNT1 downregulation decreased cell proliferation and invasion, inhibited WNT/β-catenin activation and affected the expression of E-cadherin and P-cadherin. MiR-34a upregulation resulted in decreased WNT1 expression. An inverse correlation between miR-34a and WNT1 expression was also observed in primary cervical SCC tissues. In addition, we found that MiR-34a could regulate an E-cadherin to P-cadherin switch (E-P cadherin switch) to inhibit cell proliferation and tumorigenesis in vitro and in vivo via inactivation of the WNT1/β-catenin pathway. Finally, we found that decreased HPV-16 E6/E7 expression resulted in miR-34a upregulation and WNT1 downregulation in Siha and Caski cells. Conclusions From our results we conclude that WNT1, as a target of miR-34a, can promote cervical SCC cell proliferation and invasion by induction of an E-P cadherin switch via the WNT1/β-catenin pathway. Our results may provide new options for the treatment of patients with cervical SCC.Keywords Cervical squamous cell carcinoma . miR-34a . WNT1 . E-cadherin . P-cadherin . Cadherin switch Electronic supplementary material The online version of this article (https://doi.

BackgroundThe large-conductance, voltage-gated, calcium (Ca (2+))-activated potassium channel (BKCa) plays an important role in regulating Ca (2+) signaling and cell physiological function, and is aberrantly expressed in some types of cancers. The present study focuses on identifying the oncogenic potential and clinical significance of BKCa in endometrial adenocarcinoma, as well as exploring the mechanistic relevance by 17β -estradiol (E2) inducing aberrant activation of MEK1/2 and ERK1/2 via BKCa.MethodsThe expression of BKCa, ERK1/2 and p-ERK1/2 were examined by immunohistochemical staining in 263 cases, including 185 primary types I endometrial cancer tissues, 38 atypical endometrial hyperplasia tissues and 40 normal endometrium tissues. Cell growth, cycle, apoptosis rate, migration and invasion was separately tested in Ishikawa cells using siRNA-BKCa and/or E2 treatment, as well as the expression of these interested proteins by western blot analysis.ResultsWe showed that expression of BKCa is significantly elevated in 185 types I endometrial adenocarcinoma tissues compared to those of the normal endometrium and atypical endometrial hyperplasia tissues. Furthermore, in vitro observations revealed that down-regulation of BKCa expression inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, suppressed cell migration and invasion in Ishakiwa cells, and decreased the expression of p-MEK1/2 and p-ERK1/2. Additionally, RNAi-mediated knockdown of BKCa attenuated the increased cellular growth and invasion, as well as the elevated expression of p-MEK1/2 and p-ERK1/2 proteins, induced by E2 stimulation. More importantly, the aberrant expression of BKCa and p-ERK1/2 were closely related with poor prognostic factors in type I endometrial cancer, and up-regulated expression of p-ERK1/2 was significantly associated with shorter disease-free survival (DFS) and overall survival (OS) and was an independent prognostic factor in type I endometrial cancer patients.ConclusionOur results demonstrated that BKCa and the key downstream effectors p-ERK1/2 could be involved in important signaling pathways in initiation and development of endometrial adenocarcinoma and may provide a new therapeutic approach for women with endometrial cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5027-9) contains supplementary material, which is available to authorized users.

There is currently a lack of research on preoperative prognostic analysis of earlystage cervical adenocarcinoma (ADC). The purpose of our study was to clarify whether preoperative serum tumor-marker levels were of prognostic value in early-stage ADC. Patients and Methods: We performed a retrospective study of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IIA1 and pathology-proven invasive ADC. We evaluated the relationship between preoperative serum tumor-marker levels and clinicopathological characteristics, and identified the relative preoperative risk factors affecting disease-free survival (DFS) and overall survival (OS). The optimal cutoff point of meaningful tumor markers was determined by the analysis of receiver operating characteristics (ROC), and the accuracy of the results was evaluated by the area under the curve (AUC). Results: Elevated carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC-Ag), alpha-fetoprotein (AFP), carbohydrate antigen 153 (CA153) and carbohydrate antigen 199 (CA199) were associated with certain clinicopathologic features of early-stage ADC. The combination of elevated serum CEA and CA125 was significantly associated with FIGO stage, body mass index (BMI) and LNM. Kaplan-Meier survival curve and Cox regression analyses revealed that CEA and CA125 might have significant prognostic implications in early-stage ADC patients, and the combination of elevated serum CEA and CA125 served as an independent predictor of early-stage ADC. The optimal cutoff point of serum CA125 for prediction DFS and OS was 32.60 U/mL and of serum CEA were 2.85 ng/mL and 2.05 ng/mL, respectively. The AUC showed that serum CEA was a moderate predictor of OS. Conclusion: The preoperative serum levels of CEA and CA125 might have significant prognostic implications in early-stage ADC patients. Combined preoperative serum CEA and CA125 levels independently predicted the prognosis of early-stage ADC.

ObjectiveIn this study, we summarize the clinical characteristics and neonatal outcomes of patients with pregnancy luteomas that were identified incidentally at cesarean section in our hospital. We also provide a review of the existing literature relating to this condition.MethodsA total of seven cases of pregnancy luteoma were enrolled from our hospital into this retrospective study between March 2013 and February 2018. We then evaluated the clinical characteristics and neonatal outcomes of these patients.ResultsAll seven patients with pregnancy luteomas found incidentally during Cesarean sections at term as a result of obstetric indications. These masses were unilateral and ranged from 2 to 10 cm in size. All patients underwent partial ovariectomies or oophorocystectomy due to presumptive benign ovarian tumors. Two patients had gestational diabetes and one patient had gestational hypertension. One patient developed hirsutism and a deepened voice. Of the seven newborns, three were girls and four were boys. Physical examinations of the newborns were normal and no virilization was detected among the infant girls.ConclusionPregnancy luteoma may be more common than expected. Better strategies are now needed to educate obstetricians about the clinical features of pregnancy luteoma so that they can avoid unnecessary surgery.

To investigate the potential factors to predict severe myelosuppression among low-risk gestational trophoblastic neoplasia (GTN) patients with single-agent methotrexate (MTX) chemotherapy. To analyze reproductive outcomes of patients with or without severe myelosuppression after achieving complete remission (CR). Patients and Methods: The retrospective study included 319 low-risk GTN patients registered from January 2008 to December 2018 in our hospital. Patients were divided into two groups according to myelosuppression grading. Their clinical data and reproductive outcomes were compared and analyzed. Results: A higher proportion of patients in group A received second-line chemotherapy than group B (P<0.001). The number of total chemotherapy courses was more in group A than group B (P=0.001), while the number of MTX chemotherapy courses was more in group B than group A (P=0.001). When the joint predictor of pretreatment albumin (ALB) was not more than 44.5 g/L, pretreatment serum creatinine (Scr) was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses was not less than four, there was a moderate predictive value. There was no significant difference of reproductive outcomes between the two groups after achieving CR. Conclusion: Although some patients developed severe myelosuppression, MTX was still the effective first-line treatment for low-risk GTN patients. Patient's pretreatment ALB was not more than 44.5 g/L, pretreatment Scr was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses not less than four could be used as combined predictors to recognize the risk of severe myelosuppression. Severe myelosuppression had no significant adverse influence on fertility after achieving CR.