MicroRNA-106b (miR-106b) was recently identified as an oncogene participating in cancer progression. Transforming growth factor β1(TGF-β1) is an indispensable cytokine regulating the local microenvironment, thereby promoting cervical cancer progression. However, the roles of miR-106b in cervical carcinoma progression and TGF-β1-involvement in the tumorigenesis of cervical cancer remain unknown. The expression of miR-106b in human cervical specimens was detected by real-time PCR analysis and in situ hybridization assay. The effect of miR-106b on cell migration was analyzed by scratch and transwell assays. TGF-β1 was used to induce cell migration. The expression of the miR-106b target gene DAB2 in human cervical tissues and cell lines were measured by qRT-PCR, western blot and immunohistochemistry. Dual-luciferase reporter assay was used to identify DAB2 as a miR-106b-directed target gene. miR-106b was frequently up-regulated in human cervical carcinoma specimens and cervical cancer cell lines. Over-expression of miR-106b significantly promoted HeLa and SiHa cells migration. Likewise, inhibition of miR-106b decreased HeLa and SiHa cells migration. The multifunctional cytokine TGF-β facilitates metastasis in cervical carcinoma. miR-106b inhibitor treatment decreased the TGF-β1-stimulated migration of HeLa and SiHa cells. DAB2, a predicted target gene of miR-106b, was inhibited by TGF-β1 partly through miR-106b and was involved in TGF-β1-induced cervical cancer cell migration. The expression of DAB2 was low in cervical cancer tissues, and negatively correlated with miR-106b expression. Finally, DAB2 was identified as a miR-106b-directed target gene by dual-luciferase reporter assay. Our data suggest that the TGF-β1/miR-106b/DAB2 axis may be involved in the pathogenesis of cervical carcinoma.
20 January 2022 in European Journal of Nuclear Medicine and Molecular Imaging
This study aimed at developing an available recurrence-free survival (RFS) model of endometrial cancer (EC) for accurate and individualized prognosis assessment. A training cohort of 520 women with EC who underwent initial surgical treatment and an external validation cohort of 445 eligible EC patients from 2006 to 2016 were analyzed retrospectively. Multivariable Cox proportional hazards regression models were used to develop nomograms for predicting recurrence. The concordance index (C-index) and the area under the receiver operating characteristic curve (AUC) were calculated to determine the discrimination of RFS prognostic scoring systems. Calibration plots were generated to examine the performance characteristics of the predictive nomograms. Regression analysis revealed that an advanced International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade 3, primary tumor diameter ≥2 cm, and positive peritoneal cytology were independent prognostic factors for RFS in EC in the training set. The nomograms estimated RFS according to these four variables, with a C-index of 0.860, which was superior to that of FIGO stage (2009 criteria), at 0.809 (), in the training cohort. Encouragingly, consistent results were observed in the validation set, with a C-index of 0.875 for the nomogram and a C-index of 0.833 for the FIGO staging (). Furthermore, the calibrations of the nomograms predicting 3- and 5-year RFS strongly corresponded to the actual survival outcome. In conclusion, this study developed an available nomogram with effective external validation and relatively appreciable discrimination and conformity for the accurate assessment of 3- and 5-year RFS in Chinese women with EC.
29 June 2023 in Therapeutics and Clinical Risk Management
Background: The role of immune checkpoint inhibitors in endometrial cancer is limited. At present, the anti-programmed cell death protein 1 (anti-PD-1) antibody is only used in patients with recurrence or metastasis. CD40 is an important immune checkpoint, which is expressed in tumor cells and immune cells, but its distribution characteristics in endometrial carcinoma have not been explored. Methods: Sixty-eight cases of primary endometrial carcinoma treated in Peking University People’s Hospital from January 2010 to December 2020 were collected, including 28 cases of poorly differentiated endometrioid adenocarcinoma, 23 cases of serous carcinoma and 17 cases of clear cell carcinoma. The relationship of CD40 expression and PD-L1 expression with their prognosis was analyzed by immunohistochemistry. Results: We found that CD40 had higher expression in non-endometrioid endometrial carcinoma, which lead to the worse prognosis. The effect of high expression of CD40 on the prognosis of endometrioid adenocarcinoma was not significantly different, and most patients with good prognosis. We found that the proportion of CD40 distribution in tumor cells and immune cells may be associated with this heterogeneity. Conclusion: The expression of CD40 in different endometrial cancers may indicate the difference prognosis, which may become a potential target for drug treatment of non-endometrioid endometrial carcinoma.