As the newest colposcopic terminology, the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) classification provides standardized interpretation of colposcopic findings. In this study, we analyzed the colposcopic accuracy and the significance of individual findings according to the 2011 IFCPC classification in 525 patients, reviewed by 13 trained colposcopists. Results show that colposcopic diagnoses are in 64.95% perfect agreement with cervical pathology, with 63.64% sensitivity and 96.01% specificity for high-grade squamous intraepithelial lesion (HSIL+). And the accuracy is reproducible across different experienced examiners. Many individual findings, especially the two new signs, inner border sign and ridge sign, are proved to have good predictive accuracy, while iodine negativity demonstrates an inferior performance. However, the distribution of three cervical transformation zone (TZ) types is heterogeneous in examiners. A comparison was also made of the findings of another two colposcopists without nomenclature training according to the Reid Colposcopic Index (RCI), modified RCI, and Swede Score. Results show that colposcopic accuracies in them are lower than in those nomenclature trained colposcopists. The 2011 IFCPC nomenclature improves colposcopic accuracy in trained colposcopists, like speaking the same language. However, the reproducibility of TZ and the predictive value of a few signs remain to be discussed.

Background Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC. Methods Gene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation. Results We observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. Conclusions The depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.

Background: Immune checkpoint blockade inhibitors have aroused great expectation on many types of tumor eradication. However, the therapeutic effect of anti-PD-L1 treatment on cervical cancer is unsatisfactory and the potential antagonist is not very clear. Here, we investigated the therapeutic effect of anti-PD-L1 in cervical tumor mouse model and identified the potential threats for anti-PD-L1 therapeutic efficacy. Results: we found that PD-L1 had a moderate expression in human and mouse cervical tumor cell lines and clinical samples compared to other tumor types and para-tumor tissue. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group even with the same genome background C57BL/6 syngeneic tumor model. The unresponsive tumors showed less immune cell infiltration and higher Tregs population induced immunosuppression activity than the responsive ones. Furthermore, we found that anti-PD-L1 autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion more significantly depressed the tumor growth rate and tumor weight than either anti-PD-L1 or anti-CD25 alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion. Conclusion: In conclusion, anti-PD-L1 therapy upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy in the immunotherapy of cervical cancer.

Background Immune checkpoint inhibitors have aroused great expectation of tumor eradication. However, the effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. Here, we investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment. Results We found that PD-L1 exhibited a moderate expression in both cervical tumor cell lines and clinical samples compared to other tumor types and the para-tumor tissue respectively. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group after five cycles of anti-PD-L1 treatment although all the mice had the same genome background. In addition, the unresponsive tumors showed less tumor necrosis area and higher immunosuppression activity induced by regulatory T cells (Tregs) population than the responsive ones. Furthermore, we found that anti-PD-L1 treatment autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion significantly depressed the tumor growth rate and tumor weight compared with either anti-PD-L1 or anti-CD25 treatment alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion. Conclusions Anti-PD-L1 treatment upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy of cervical cancer.

BackgroundSmall nucleolar RNA host gene 25 (SNHG25), a long-noncoding RNA, has been well studied in epithelial ovarian cancer. Yet, the specific functions of SNHG25 in endometrial cancer (EC) have not been researched. In this study, we proposed to expose the clinic significance of SNHG25 in EC, and then unravel the regulatory activity of SNHG25 on the tumor-associated phenotype of EC. More interestingly, the possible molecular events occurred when SNHG25 executives its function in EC were explored thoroughly. MethodsWe measured genes expression applying quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined employing loss-of-function experiments. What’s more, we unveiled the regulatory mechanisms among SNHG25, microRNA-497-5p and fatty acid synthase (FASN) with the application of luciferase reporter assay and RNA Immunoprecipitation. ResultsWe verified a high level of SNHG25 in EC through TCGA dataset and our own cohort. Patients with a high SNHG25 level featured shorter overall survival in contrast to patients with a low SNHG25 level. SNHG25 deficient caused tumor-repressing actions in EC cells by decreasing cell proliferation, migration and invasion and promoting cell apoptosis. Furthermore, we certified the function of SNHG25 depletion in impairing tumor growth in vivo. With respect to the mechanisms, SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Striking, the decrease of miR-497-5p or increase of FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. ConclusionsDepleted SNHG25 hampered the oncogenicity of EC by targeting miR-497-5p/FASN axis. The newly certified SNHG25/miR-497-5p/FASN pathway may potentially have usefulness as a promising target for molecular targeted management.