Developing a diagnostic model for predicting prostate cancer: a retrospective study based on Chinese multicenter clinical data.

ABSTRACT: The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.

[Nur77 inhibits the proliferation of prostate cancer cells].

OBJECTIVE: To study the effects of Nur77 on prostate cancer (PCa) cell growth and its potential value in the treatment of PCa. METHODS: We detected the expression of the NUR77 protein in human PCa tissues and cells by Western blot and determined the effects of Nur77 on the proliferation and apoptosis of the PCa cells by flow cytometry. RESULTS: Nur77 and AR were expressed in the human PCa tissue and cells, and overexpressed NUR77 inhibited the proliferation and cell cycle progression of the PCa LNCaP cells. The small-molecule receptor agonists cytosporone B and DIMC of Nur7 significantly suppressed the growth and induced the apoptosis of the PCa LNCaP cells. CONCLUSIONS: Nur77 inhibits the proliferation and induces the apoptosis of PCa cells, and is expected to be a potential molecular target for the treatment of PCa.

[The transcription factor NF-kB1 regulates miR-195 expression in prostate cancer].

OBJECTIVE: To investigate the regulatory effect of the transcription factor NF-kB1 on the expression of miR-195 in prostate cancer (PCa). METHODS: We analyzed the possibility of NF-kB1 binding to the miR-195 promoter and the expression of NF-kB1 in PCa using the JASPAR and Oncomine databases, respectively, and determined the expressions of NF-kB1 and miR-195 in PCa cells by real-time quantitative PCR after inhibiting the former by interfering RNA targeting NF-kB1. We detected the activity of the luciferase reporter gene after constructing its gene plasmid in the miR-195 promoter region and having it co-transfected with the NF-kB1 plasmid. Then we analyzed the correlation between the expressions of miR-195 and NF-kB1 in the prostate tissue. RESULTS: NF-kB1 was overexpressed in PCa. After inhibition of the expression of NF-kB1, that of miR-195 was increased in PC-3 and DU-145 cell lines, with a negative correlation between the NF-kB1 and miR-195 expressions in the PCa tissue. The results of luciferase reporter gene assay showed direct binding of NF-kB1 to the miR-195 promoter zone. CONCLUSIONS: NF-kB1 regulates the expression of miR-195 in prostate cancer.

miR-143 inhibits renal cell carcinoma cells metastatic potential by suppressing ABL2.

Although micro RNA (miRNA) expression profiles are widely investigated in renal cell carcinoma (RCC), their potential roles for affecting RCC initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs inhuman metastatic RCC tissues based on Gene Expression Omnibus (GSE37989). We further validated them iRNAs expression data in the largest clinical dataset: The Cancer Genome Atlas (TCGA). And cell adhesion and migration abilities and epithelial me senchymal transition (EMT) related proteins were assessed in both normal and tumor RCC cell lines. We suggest that hsa-miR-143 is a potential tumor suppressor in RCC as its down regulation positively correlated with adverse prognosis. Biologically, cell adhesion, migration, and EMT were dramatically inhibited by miR-143. Mechanistically, we found that miR-143 targets ABL proto-oncogene 2 (ABL2), which was also found to be an indicator for poor survival in TCGA database. Our results have important implications in understanding functions of miRNAs in metastatic RCC and will provide a basis for further clinical application.

Diagnostic Performance of PET/CT Using 18F-FACBC in Prostate Cancer: A Meta-Analysis.

Background: Diagnostic performance of PET/CT using 18F-fluciclovine (18F-FACBC) in patients with prostate cancer (PCa) has been evaluated in only a few studies. There is no consensus on the diagnostic value of 18F-FACBC PET/CT in PCa recurrence or metastasis (except for bone metastasis), the primary diagnosis of the lesion. Hence, a meta-analysis was conducted to evaluate the performance of 18F-FACBC PET/CT. Methods: The literature published from June 2015 to June 2019 on using 18F-FACBC PET/CT for the diagnosis of PCa was retrieved from PubMed and EMBASE. Pooled sensitivity (Sen), specificity (Spe), positive and negative likelihood ratios (LR+ and LR-), area under the curve (AUC), and diagnostic odds ratio (DOR) of 18F-FACBC PET/CT in patients with PCa were calculated. An SROC map was made, and a meta-regression analysis was carried out. A Fagan plot and likelihood ratio dot plot were drawn. Sensitivity and funnel plot analysis were made. Meta-disc, Review Manager 5.3, and STATA 13 were used for the meta-analysis. Results: A total of nine articles met the strict criteria for diagnostic meta-analysis, which included 363 patients and 345 lesions. Pooled Sen, Spe, LR+, LR-, DOR were 0.88, 0.73, 3.3, 0.17, and 20, respectively. Lesions detected on the PET/CT image included primary lesions and metastases. For the lesion, the doctors considered the abnormal part as a lesion on the PET/CT image by their own experience and expertise, including primary lesions and metastases. For the patient, patients who participated in the trial can be diagnosed as PCa through 18F-FACBC. Conclusion: This study comprehensively evaluated the diagnostic value of 18F-FACBC PET/CT on PCa. Our analysis suggests that 18F-FACBC PET/CT is a valuable agent in diagnosing PCa. More studies are needed for further validation.

[Establishment of enzalutamide-resistant human prostate cancer cell lines and screening of lncRNA and mRNA expression profiles].

OBJECTIVE: To establish enzalutamide-resistant human prostate cancer cell lines and screen out the lncRNA and mRNA expression profiles associated with enzalutamide resistance. METHODS: Human prostate cancer cell lines LNCAP and C4-2B were cultured with 10 µmol/L enzalutamide for 6 months in vitro for the establishment of enzalutamide-resistant subclones LNCAP-ENZA and C4-2B-ENZA. The IC50 value and enzalutamide resistance index of each cell line were examined by MTT assay, the expressions of enzalutamide-related genes FL-AR, AR-V7 and HnRNPA1 were determined by Western blot, and the lncRNA and mRNA differential expressions of C4-2B and C4-2B-ENZA were detected by high-throughout lncRNA microarray. RESULTS: Compared with LNCAP and C4-2B, the IC50 values of enzalutamide-resistant subclones LNCAP-ENZA (60.83 µmol/L) and C4-2B-ENZA (88.32 µmol/L) were increased significantly (P < 0.05) and the enzalutamide-resistance indexes of the LNCAP-ENZA and C4-2B-ENZA cells were 4.94 and 4.67, respectively. The expressions of AR-V7 and HnRNPA1 were markedly up-regulated in the LNCAP-ENZA and C4-2B-ENZA cells as compared with those in the LNCAP and C4-2B cells, but that of FL-AR showed no significant change. A total of 1 440 lncRNAs and 1 236 mRNAs were identified as differentially expressed in the C4-2B-ENZA cells. CONCLUSIONS: Enzalutamide -resistant human prostate cancer cell subclones LNCAP-ENZA and C4-2B-ENZA were successfully established and enzalutamide resistance-associated lncRNA and mRNA were identified, which may provide some molecular evidence for the management of enzalutamide-resistant human prostate cancer.

miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer.

MicroRNAs (miRNAs) act as tumor promoters or tumor suppressors in different human malignancies. In the current study, using an Agilent miRNA microarray, miR­30a was found to be a significantly downregulated miRNA in castration­resistant prostate cancer (CRPC) tissues, compared with androgen­dependent prostate cancer tissues. Aberrant expression of cyclin E2 (CCNE2) has been reported in a variety of types of cancer including prostate cancer, and correlates with clinical outcome. The purpose of the current study was to determine the functions of miR­30a in CRPC cell lines and identify whether CCNE2 was regulated by miR­30a. To analyze the associations between miR­30a and CCNE2 expression levels, pathological specimens were collected, and reverse transcription­quantitative polymerase chain reaction and immunohistochemical staining were conducted. The effect of miR­30a overexpression on CRPC cell lines and the predicted target gene, CCNE2, were evaluated by MTT assay, flow cytometry, tumor formation, luciferase reporter assay and western blotting. miR­30a overexpression resulted in a significant suppression of cell growth in vitro, and reduced tumorigenicity in vivo. miR­30a repressed the expression of CCNE2 through binding to its 3'­untranslated region. CCNE2 was observed to be overexpressed in patients with CRCP and had an approximately inverse correlation with the level of miR­30a. The results suggest that miR­30a may function as a novel tumor suppressor in CRPC. Its anti­oncogenic activity may occur by the reduced expression of a distinct cell cycle protein, CCNE2.

[Expression of SRD5A1 and its prognostic role in prostate cancer: Analysis based on the data-mining of ONCOMINE].

OBJECTIVE: To explore the expression of I-5α-reductase (SRD5A1)and its prognostic role in prostate cancer . METHODS: Data about SRD5A1 were retrieved from the ONCOMINE database and the role of SRD5A1 in prostate cancer was analyzed. RESULTS: Totally, 992 studies of different types relevant to the expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1 expression was statistically significant in 239 of the studies, overexpressed in 157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of SRD5A1 in prostate cancer and normal tissues, which was significantly higher in the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1 expression was high in primary prostate cancer and increased with its metastasis (P<0.0 5). Two of the studies with prognostic data showed a higher rate of postoperative biochemical recurrence and a higher total mortality rate in the patients with a high than in those with a low expression of SRD5A1 (P<0.05). CONCLUSIONS: SRD5A1 is highly expressed in prostate cancer, especially in metastatic and castration-resistant prostate cancer and its expression is associated with the prognosis of prostate cancer, which may be an important target of medication for prostate cancer.

[Expression of long noncoding RNA LINC01358 in prostate cancer and its effect on the proliferation and migration of prostate cancer cells].

OBJECTIVE: To explore the expression of long noncoding RNA (lncRNA) LINC01358 in prostate cancer (PCa) and its effect on the proliferation and migration of PCa cells. METHODS: The lncRNA array was used to screen differentially expressed lncRNAs in PCa and the corresponding carcinoma-adjacent normal tissues from 3 patients. The expressions of LINC01358 in the primary PCa, metastatic PCa, and carcinoma-adjacent tissues were compared using the PCa dataset of the Memorial Sloan Kettering Cancer Center (MSKCC). The data obtained were validated by determining the expression of LINC01358 in the PCa and carcinoma-adjacent tissues of another 10 patients by quantitative real time PCR (qRT-PCR). The effects of lncRNA LINC01358 on the proliferation of DU145 cells and migration of PCa cells were detected by MTT and Transwell assay, respectively. RESULTS: Totally, 79 differentially expressed lncRNAs in the lncRNA array, 36 highly and the other 43 lowly expressed in the PCa tissue. LINC01358 was up-regulated in the cancerous tissue. According to the MSKCC data, the LINC01358 expression was markedly higher in metastatic PCa (5.81±0.19, n = 19) and primary PCa (5.47±0.04, n = 131) than in the PCa-adjacent tissue (5.15±0.07, n = 29) and significantly correlated with postoperative biochemical relapse of the malignancy (P<0.05). qRT-PCR indicated a remarkably higher expression of LINC01358 in the PCa than in the carcinoma-adjacent tissue (6.02±1.12 vs 3.21±0.21, P<0.05). Transfection of the DU145 cells with siRNA significantly decreased the level of LINC01358 and inhibited the proliferation and migration of the PCa cells. CONCLUSIONS: LINC01358 is highly expressed in the PCa tissue and knockdown of LINC01358 may inhibit the proliferation and migration of PCa cells. LncRNA LINC01358 may be involved in the development and progression of PCa and become an index for the early diagnosis as well as a new target for the gene therapy of the malignancy.

[3D versus 2D laparoscopic radical prostatectomy for the treatment of prostate cancer].

OBJECTIVE: To compare the outcomes and complications of 3D versus 2D laparoscopic radical prostatectomy ( LRP) in the treatment of prostate cancer. METHODS: We retrospectively reviewed 18 cases of prostate cancer treated by 3D LRP and another 32 by 2D LRP. We compared the general data, intraoperative blood loss, postoperative drainage time and hospital stay, Gleason scores, and incidence of complications between the two groups of patients. RESULTS: All the operations were successful and none was transferred to open surgery. The two groups of patients were similar in terms of age, body mass index, Gleason scores, and clinical stages. However, compared with the 2D LRP group, the 3D LRP group showed significantly shorter operation time ([180.2 ± 69.1] vs [118.3 ± 55.1] min, P < 0.01), less blood loss ([236.5 ± 60.6] vs [89.1 ± 35.2] ml, P < 0.01), less postoperative drainage time ([7.1 ± 1.1] vs [5.3 ± 2.1] d, P < 0.01), shorter postoperative hospital stay ([20.2 ± 5.5] vs [14.4 ± 7.2] d, P < 0.01), and lower incidence of perioperative complications (3.1% vs 0, P < 0.01). The incisal margin was pathologically negative in both groups and urinary incontinence was found in neither at 6 months after surgery (P > 0.05). CONCLUSION: 3D LRP, with its advantages of shorter operative time, faster recovery, and better outcomes than 2D LRP in the treatment of prostate cancer, deserves general application in lower-level hospitals.

[Preventive administration of antibiotics to patients with benign prostatic hyperplasia before urodynamic examination].

OBJECTIVE: To discuss the effect and safety of preventive administration of antibiotics to patients with benign prostatic hyperplasia (BPH) before urodynamic examination. METHODS: A total of 256 BPH patients to undergo urodynamic examination were randomly divided into a control group (n = 118) and a trial group (n = 138). The former received no pre-treatment while the latter were given cefoxitin sodium iv at 1.0 g 30 minutes before complete urodynamic examination. Then we compared the incidence rates of urinary tract infection between the two groups. RESULTS: Statistically significant differences were found in the incidence rate of urinary tract infection between the control and trial groups (20.3% [24/118] vs 7.3% [10/138], P < 0.01), as well as in those with diabetes mellitus (6.7% [3/45] vs 23.5% [8/34], P < 0.05), those with residual urine > 50 ml (5.4% [3/56] vs 18.5% [10/54], P < 0.05), and those with both diabetes mellitus and residual urine (9.5% [2/21] vs 44.4% [8/18], P < 0.05). Only 3 patients (2.2%) in the trial group had mild adverse drug reactions. CONCLUSION: For BPH patients, particularly those with diabetes mellitus and residual urine, preventive administration of antibiotics before urodynamic examination is safe and can effectively protect the patients against urinary tract infection.

Contribution of HOGG1 Ser³²6Cys polymorphism to the development of prostate cancer in smokers: meta-analysis of 2779 cases and 3484 controls.

The HOGG1 gene catalyzes the excision of modified bases and removal of DNA damage adducts. It may play an important role in the prevention of carcinogenesis. Ser³²6Cys polymorphism localizes in exon 7 of the hOGG1 gene. It takes the form of an amino acid substitution, from serine to cysteine, in codon 326. Several epidemiological association studies have been conducted on this polymorphism and its relationship with the risk of prostate cancer. However, results have been conflicting. To resolve this conflict, we conducted a meta-analysis on the association between this polymorphism and prostate cancer, taking into account race, country, sources of controls, and smoking status. A total of nine studies covering 2779 cases and 3484 controls were included in the current meta-analysis. Although no significant association was found between hOGG1 Ser³²6Cys polymorphism and prostate cancer susceptibility in the pooled analysis, individuals with Ser/Cys+Cys/Cys genotypes were found to have greater risk of prostate cancer if they were also smokers (OR = 2.66, 95% CI = 1.58-4.47) rather than non-smokers (OR = 2.18, 95% CI = 1.13-4.19), compared with those with Ser/Ser genotype. In conclusion, our meta-analysis demonstrates that hOGG1 Ser³²6Cys polymorphism is a risk factor for prostate cancer in smokers. Further studies are needed to confirm this relationship.

[Erectile function in male kidney transplant recipients and effects of different methods of renal arterial anastomosis].

OBJECTIVE: To evaluate erectile function in men with renal failure before and after kidney transplantation and the effects of different methods of renal arterial anastomosis. METHODS: Fifty-five married males, aged 22-50 years, who had received kidney transplantation at least one year before and whose serum creatinine was under 200 micromol/L , were selected in the study. The end-to-end revascularization to the internal iliac artery was accomplished in 39 of them, and the end-to-side revascularization to the external iliac artery was conducted in 16. Their erectile function was investigated according to the International Index of Erectile Function-5 (IIEF-5) before kidney transplantation and 3, 6 and 9 months after it. The effects of different methods of renal arterial anastomosis were evaluated and hypophyseal hormones determined in 25 of them. RESULTS: IIEF-5 was higher in the patients 3, 6 and 9 months after transplantation than before it (P < 0.05) and 6 and 9 months after transplantation than 3 months after it (P < 0.05) , so was it in the patients with less than 12 months hemodialysis than those with over 12 months (P < 0.05) and in the patients with end-to-side revascularization to the external iliac artery than those with end-to-end revascularization to the internal iliac artery (P < 0.05). The differences between the level of hypophyseal hormones and that of sex hormones before transplantation were significant (P < 0.05). CONCLUSION: Erectile function and the level of hypophyseal hormones were improved after kidney transplantation, and the patients who received end-to-side revascularization to the external iliac artery experienced better erectile function recovery than those who underwent end-to-end revascularization to the internal iliac artery.