Forkhead box K1 (FOXK1) is a member of the FOX transcription factor family and plays an important role in the development of several tumors. However, the role of FOXK1 in the progression of prostate cancer remains unknown. Thus, the objectives of this study were to detect the expression of FOXK1 in prostate cancer and to examine its role in prostate cancer cells. We found that the expression of FOXK1 at both the mRNA and protein levels was significantly upregulated in human prostate cancer cell lines. In addition, the downregulation of FOXK1 obviously inhibited the cell proliferation of prostate cancer cells in vitro and attenuated tumor growth in a xenograft model in vivo. Furthermore, knockdown of FOXK1 suppressed the migration and invasion of prostate cancer cells, and prevented the EMT phenotype through upregulating the expression of E-cadherin, as well as downregulating the expression of N-cadherin in prostate cancer cells. Mechanistically, knockdown of FOXK1 efficiently downregulated the expression levels of β-catenin, c-myc, and cyclin D1 in PC-3 cells. Overall, our results demonstrated that knockdown of FOXK1 inhibited the proliferation and metastasis of prostate cancer, at least in part, through suppressing the Wnt/β-catenin signaling pathway. Therefore, these results suggest that FOXK1 may be a potential therapeutic target for human prostate cancer.

Background: Bipolar transurethral enucleation and resection of the prostate in saline has recently been considered as a safe and technically feasible endoscopic procedure for symptomatic benign prostatic hyperplasia. However, it has not been accepted widely because of the perception of technical difficulty. Methods: A retrospective data review was performed of the first consecutive 100 patients who had undergone bipolar transurethral enucleation and resection of prostatic adenoma. Operative outcome, complications, ratio of conversion to conventional transurethral resection of the prostate and efficiency of tissue enucleation and resection were used to assess the learning curve. Results: Bipolar transurethral enucleation and resection of the prostate was successfully performed in 83 patients. The mean operative time was 117.5 min, and the mean indwelling catheterization was 3.3 ± 1.9 days. After 6 months, maximum urinary flow was 21.34 ± 4.09 ml/s, IPSS was 9.66 ± 2.64, and quality of life was 2.31 ± 0.92 with a residual prostate volume of 35.29 ± 17.57 ml. Regarding the learning curve, the ratio of conversion to conventional bipolar transurethral resection of the prostate decreased after 30 cases, and the efficiency of enucleation and resection increased significantly with accumulative experience after 50 cases. Conclusions: The current results established that bipolar transurethral enucleation and resection of the prostate in saline is a safe and reproducible procedure.

Efforts at finding potential biomarkers of tolerance after kidney transplantation have been hindered by limited sample size, as well as the complicated mechanisms underlying tolerance and the potential risk of rejection after immunosuppressant withdrawal. In this work, three different publicly available genome-wide expression data sets of peripheral blood lymphocyte (PBL) from 63 tolerant patients were used to compare 14 different machine learning models for their ability to predict spontaneous kidney graft tolerance. We found that the Best Subset Selection (BSS) regression approach was the most powerful with a sensitivity of 91.7% and a specificity of 93.8% in the test group, and a specificity of 86.1% and a sensitivity of 80% in the validation group. A feature set with five genes (HLA-DOA, TCL1A, EBF1, CD79B, and PNOC) was identified using the BSS model. EBF1 downregulation was also an independent factor predictive of graft rejection and graft loss. An AUC value of 84.4% was achieved using the two-gene signature (EBF1 and HLA-DOA) as an input to our classifier. Overall, our systematic machine learning exploration suggests novel biological targets that might affect tolerance to renal allografts, and provides clinical insights that can potentially guide patient selection for immunosuppressant withdrawal.

Objective: To investigate the association between graft-derived cell-free DNA and pretransplantation clinical variables, and to determine whether the former could be used as a novel biomarker to predict renal function. Methods: A total of 87 recipients who underwent primary kidney transplantation were recruited to the study. For each recipient, 10 mL peripheral blood was collected on days 1, 7, 14-20, and 30-45 after transplantation. The fractional abundance of graft-derived cell-free DNA was determined using droplet digital polymerase chain reaction. Results: For most recipients, graft-derived cell-free DNA fraction values were significantly elevated on the first day after transplantation, followed by a rapid decline, and reaching baseline values of graft-derived cell-free DNA fraction in the range of <1% at 7 days. Statistical analysis showed that longer cold ischemia time was significantly associated with higher graft-derived cell-free DNA fraction values (P = 0.02). Moreover, we also found that graft-derived cell-free DNA fraction values among recipients with delayed graft function were significantly higher than those of recipients without delayed graft function on the first day after transplantation. Kaplan-Meier analysis showed that recipients who had a graft-derived cell-free DNA fraction value of <1% at 7 days had a significantly lower probability of an estimated glomerular filtration rate ≤60 mL/min/1.73 m 2 at 90 days. Using a random forest regression model, the predicted values of estimated glomerular filtration rate at 90 days were almost the same as the actual values. Conclusions: Our findings suggest that graft-derived cell-free DNA might be used as a novel biomarker to predict delayed graft function and renal function.

Graft-derived cell-free DNA (GcfDNA) is a promising non-invasive biomarker for detecting allograft injury. In this study, we aimed to evaluate the efficacy of programmed monitoring of GcfDNA for identifying BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients. We recruited 158 kidney transplant recipients between November 2020 and December 2021. Plasma GcfDNA was collected on the tenth day, first month, third month, and sixth month for programmed monitoring and one day before biopsy. ΔGcfDNA (cp/mL) was obtained by subtracting the baseline GcfDNA (cp/mL) from GcfDNA (cp/mL) of the latest programmed monitoring before biopsy. The receiver operating characteristic curve showed the diagnostic performance of GcfDNA (cp/mL) at biopsy time and an optimal area under the curve (AUC) of 0.68 in distinguishing pathologically proven BKPyVAN from pathologically unconfirmed BKPyVAN. In contrast, ΔGcfDNA (cp/mL) had a sensitivity and specificity of 80% and 84.6%, respectively, and an AUC of 0.83. When distinguishing clinically diagnosed BKPyVAN from clinical excluded BKPyVAN, the AUC of GcfDNA (cp/mL) was 0.59 at biopsy time, and ΔGcfDNA (cp/mL) had a sensitivity and specificity of 81.0% and 76.5%, respectively, and an AUC of 0.81. Plasma ΔGcfDNA (cp/mL) was not significantly different between TCMR [0.15 (0.08, 0.24) cp/mL] and pathologically proven BKPyVAN[0.34 (0.20, 0.49) cp/mL]. In conclusion, we recommend programmed monitoring of plasma GcfDNA levels after a kidney transplant. Based on our findings from the programmed monitoring, we have developed a novel algorithm that shows promising results in identifying and predicting BKPyVAN.