As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.

Objective. To develop and internally validate nomograms based on multiparametric magnetic resonance imaging (mpMRI) to predict prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in patients with a previous negative prostate biopsy. Materials and Methods. The clinicopathological parameters of 231 patients who underwent a repeat systematic prostate biopsy and mpMRI were reviewed. Based on Prostate Imaging and Reporting Data System, the mpMRI results were assigned into three groups: Groups “negative,” “suspicious,” and “positive.” Two clinical nomograms for predicting the probabilities of PCa and csPCa were constructed. The performances of nomograms were assessed using area under the receiver operating characteristic curves (AUCs), calibrations, and decision curve analysis. Results. The median PSA was 15.03 ng/ml and abnormal DRE was presented in 14.3% of patients in the entire cohort. PCa was detected in 75 patients (32.5%), and 59 (25.5%) were diagnosed with csPCa. In multivariate analysis, age, prostate-specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE), and mpMRI finding were significantly independent predictors for PCa and csPCa (all p < 0.01). Of those patients diagnosed with PCa or csPCa, 20/75 (26.7%) and 18/59 (30.5%) had abnormal DRE finding, respectively. Two mpMRI-based nomograms with super predictive accuracy were constructed (AUCs = 0.878 and 0.927, p < 0.001), and both exhibited excellent calibration. Decision curve analysis also demonstrated a high net benefit across a wide range of probability thresholds. Conclusion. mpMRI combined with age, PSA, PV, and DRE can help predict the probability of PCa and csPCa in patients who underwent a repeat systematic prostate biopsy after a previous negative biopsy. The two nomograms may aid the decision-making process in men with prior benign histology before the performance of repeat prostate biopsy.

Objective: Previous studies have demonstrated that prostate-specific antigen density (PSAD) may aid in predicting Gleason grade group (GG) upgrading and pathological upstaging in patients with prostate cancer (PCa). However, the differences and associations between patients with apex prostate cancer (APCa) and non-apex prostate cancer (NAPCa) have not been described. The aim of this study was to explore the different roles of PSAD in predicting GG upgrading and pathological upstaging between APCa and NAPCa. Patients and Methods: Five hundred and thirty-five patients who underwent prostate biopsy followed by radical prostatectomy (RP) were enrolled. All patients were diagnosed with PCa and classified as either APCa or NAPCa. Clinical and pathological variables were collected. Univariate, multivariate, and receiver operating characteristic (ROC) analyses were performed. Results: Of the entire cohort, 245 patients (45.8%) had GG upgrading. Multivariate analysis revealed that only PSAD (odds ratio [OR]: 4.149, p < 0.001) was an independent, significant predictor of upgrading. A total of 262 patients (49.0%) had pathological upstaging. Both PSAD (OR: 4.750, p < 0.001) and percentage of positive cores (OR: 5.108, p = 0.002) were independently significant predictors of upstaging. Of the 374 patients with NAPCa, 168 (44.9%) displayed GG upgrading. Multivariate analysis also showed PSAD (OR: 8.176, p < 0.001) was an independent predictor of upgrading. Upstaging occurred in 159 (42.5%) patients with NAPCa, and PSAD (OR: 4.973, p < 0.001) and percentage of positive cores (OR: 3.994, p = 0.034) were independently predictive of pathological upstaging. Conversely, of the 161 patients with APCa, 77 (47.8%) were identified with GG upgrading, and 103 (64.0%) patients with pathological upstaging. Multivariate analysis demonstrated that there were no significant predictors, including PSAD, for predicting GG upgrading (p = 0.462) and pathological upstaging (p = 0.100). Conclusions: PSAD may aid in the prediction of GG upgrading and pathological upstaging in patients with PCa. However, this may only be practical in patients with NAPCa but not with APCa. Additional biopsy cores taken from the prostatic apex region may help improve the accuracy of PSAD in predicting GG upgrading and pathological upstaging after RP.