S100A14 inhibits cell growth and epithelial-mesenchymal transition (EMT) in prostate cancer through FAT1-mediated Hippo signaling pathway.

Prostate cancer (PCA) is an epithelial malignant tumor occurring in the prostate gland. It is the second most common male cancer in the world and one of the top five cancer deaths in men. To combat this disease, it is needed to identify important tumor suppressor genes and elucidate the molecular mechanisms. S100 calcium-binding protein A14 (S100A14), a member of the S100 family, is located on chromosome 1q21.3 and contains an EF-hand motif that binds calcium. S100A14 is involved in a variety of tumor biological processes in several types of cancers. Its expression level and related biological functions are tissue or tumor specific. However, its possible effects on prostate cancer are still unclear. Herein, we found the low expression of S100A14 in human prostate cancer tissues and cell lines. S100A14 suppressed the proliferation of prostate cancer cells and promoted cell apoptosis. Additionally, S100A14 suppressed the motility and EMT processes of prostate cancer cells. We further found S100A14 promoted the expression of FAT1 and activated the Hippo pathway, which, therefore, suppressed the prostate cancer progression. The in vivo assays confirmed that S100A14 suppressed tumor growth of prostate cancer cells through FAT1-mediated Hippo pathway in mice. In conclusion, we clarified the mechanism underlying S100A14 suppressing prostate cancer progression and, therefore, we thought S100A14 could serve as a tumor suppressor protein.

MRI-Based Nomogram of Prostate Maximum Sectional Area and Its Zone Area for Prediction of Prostate Cancer.

OBJECTIVE: To reduce unnecessary prostate biopsies, we designed a magnetic resonance imaging (MRI)-based nomogram prediction model of prostate maximum sectional area (PA) and investigated its zone area for diagnosing prostate cancer (PCa). METHODS: MRI was administered to 691 consecutive patients before prostate biopsies from January 2012 to January 2020. PA, central gland sectional area (CGA), and peripheral zone sectional area (PZA) were measured on axial T2-weighted prostate MRI. Multivariate logistic regression analysis and area under the receiver operating characteristic (ROC) curve were performed to evaluate and integrate the predictors of PCa. Based on multivariate logistic regression coefficients after excluding combinations of collinear variables, three models and nomograms were generated and intercompared by Delong test, calibration curve, and decision curve analysis (DCA). RESULTS: The positive rate of PCa was 46.74% (323/691). Multivariate analysis revealed that age, PSA, MRI, transCGA, coroPZA, transPA, and transPAI (transverse PZA-to-CGA ratio) were independent predictors of PCa. Compared with no PCa patients, transCGA (AUC = 0.801) was significantly lower and transPAI (AUC = 0.749) was significantly higher in PCa patients. Both of them have a significantly higher AUC than PSA (AUC = 0.714) and PV (AUC = 0.725). Our best predictive model included the factors age, PSA, MRI, transCGA, and coroPZA with the AUC of 0.918 for predicting PCa status. Based on this predictive model, a novel nomogram for predicting PCa was conducted and internally validated (C-index = 0.913). CONCLUSIONS: We found the potential clinical utility of transCGA and transPAI in predicting PCa. Then, we firstly built the nomogram based on PA and its zone area to evaluate its diagnostic efficacy for PCa, which could reduce unnecessary prostate biopsies.

The roles of MRI-based prostate volume and associated zone-adjusted prostate-specific antigen concentrations in predicting prostate cancer and high-risk prostate cancer.

Prostate biopsies are frequently performed to screen for prostate cancer (PCa) with complications such as infections and bleeding. To reduce unnecessary biopsies, here we designed an improved predictive model of MRI-based prostate volume and associated zone-adjusted prostate-specific antigen (PSA) concentrations for diagnosing PCa and risk stratification. Multiparametric MRI administered to 422 consecutive patients before initial transrectal ultrasonography-guided 13-core prostate biopsies from January 2012 to March 2018 at Fujian Medical University Union Hospital. Univariate and multivariate logistic regression analyses and determination of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was performed to evaluate and integrate the predictors of PCa and high-risk prostate cancer (HR-PCa). The detection rates of PCa was 43.84% (185/422). And the detection rates of HR-PCa was 71.35% (132/185) in PCa patients. Multivariate analysis revealed that prostate volume(PV), PSA density(PSAD), transitional zone volume(TZV), PSA density of the transitional zone(PSADTZ), and MR were independent predictors of PCa and HR-PCa. PSA, peripheral zone volume(PZV) and PSA density of the peripheral zone(PSADPZ) were independent predictors of PCa but not HR-PCa. The AUC of our best predictive model including PSA + PV + PSAD + MR + TZV or PSA + PV + PSAD + MR + PZV was 0.906 for PCa. The AUC of the best predictive model of PV + PSAD + MR + TZV was 0.893 for HR-PCa. In conclusion, our results will likely improve the detection rate of prostate cancer, avoiding unnecessary prostate biopsies, and for evaluating risk stratification.