Univariable and multivariable mendelian randomization study revealed the modifiable risk factors of urolithiasis.

BACKGROUND: Urolithiasis is a common urological disease with increasing incidence worldwide, and preventing its risk poses significant challenges. Here, we used Mendelian randomization (MR) framework to genetically assess the causal nature of multifaceted risk factors on urolithiasis. METHODS: 17 potential risk factors associated with urolithiasis were collected from recently published observational studies, which can be categorized basically into lifestyle factors and circulating biomarkers. The instrumental variables of risk factors were selected from large-scale genome-wide association studies (N ≤ 607,291). Summary-level data on urolithiasis were obtained from UK Biobank (UKB) (3,625 cases and 459,308 noncases) and the FinnGen consortium (5,347 cases and 213,445 noncases). The univariable and multivariable MR analyses were applied to evaluate the causal, independent effect of these potential risk factors upon urolithiasis. Effects from the two consortia were combined by the meta-analysis methods. RESULTS: Higher genetically predicted sex hormone-binding globulin (SHBG, OR, 0.708; 95% CI, 0.555 to 0.903), estradiol (OR, 0.179; 95% CI, 0.042 to 0.751), tea intake (OR, 0.550; 95% CI, 0.345 to 0.878), alcoholic drinks per week (OR, 0.992; 95% CI, 0.987 to 0.997), and some physical activity (e.g., swimming, cycling, keeping fit, and bowling, OR, 0.054; 95% CI, 0.008 to 0.363) were significantly associated with a lower risk of urolithiasis. In the Multivariate Mendelian Randomization (MVMR) analyses, the significant causal associations between estradiol, SHBG, tea intake, and alcoholic drinks per week with urolithiasis were robust even after adjusting for potential confounding variables. However, the previously observed causal association between other exercises and urolithiasis was no longer significant after adjusting for these factors. CONCLUSIONS: The univariable and multivariable MR findings highlight the independent and significant roles of estradiol, SHBG, tea intake, and alcoholic drinks per week in the development of urolithiasis, which might provide a deeper insight into urolithiasis risk factors and supply potential preventative strategies.

[Penile cancer with perineural invasion is more prone to postoperative recurrence].

OBJECTIVE: To explore the correlation between perineural invasion and postoperative recurrence in patients surgically treated for penile cancer. METHODS: We conducted a retrospective analysis of the clinical data on 18 penile cancer patients surgically treated in our hospital from January 2018 to December 2021, 8 with postoperative recurrence (the recurrence group) and the other 10 without (the non-recurrence control group). We compared the two groups of patients in the age of onset, tumor-node-metastasis (TNM) stages, American Joint Committee on Cancer (AJCC) prognosis stages, surgical methods, perineural invasion and recurrence time. We analyzed the differences in postoperative recurrence using the Kaplan Meier plotted survival curve and in independent risk factors in predicting postoperative recurrence using the ROC curve. RESULTS: Compared with the non-recurrence controls, the patients in the recurrence group had a significantly older age of onset (P=0.0411) and severer perineural invasion (P<0.001), and those with perineural invasion had a shorter recurrence time (P<0.001), which was an independent risk factor for postoperative recurrence. The areas under the ROC curves for perineural invasion and age were 0.885 and 0.213, respectively. CONCLUSION: Penile cancer with perineural invasion is more prone to and perineural invasion is an independent risk factor for postoperative recurrence of the malignancy.

Survival Analysis and a Novel Nomogram Model for Progression-Free Survival in Patients with Prostate Cancer.

Background: This study sought to perform a survival analysis and construct a prognostic nomogram model based on the Gleason grade, total prostate-specific antigen (tPSA), alkaline phosphate (ALP), and TNM stage in patients with prostate cancer (PCa). Methods: The progression-free survival (PFS) of 255 PCa patients was analyzed in this study. The prognostic value of tPSA and ALP was evaluated using the Kaplan-Meier survival curves and Cox regression analysis, and a nomogram model based on the Gleason grade, tPSA, ALP, and TNM stage was further established for PFS prediction in PCa patients. Results: PCa patients with different Gleason grades, tPSA and ALP levels, and TNM stages presented distinct PFS. The Gleason grade, tPSA, ALP, and TNM stage were four independent prognostic indicators. The C-index of the established nomogram was 0.705 for PFS in the test cohort and 0.687 for the validation cohort, and the calibration curves indicated a good consistency between predicted and actual PFS in PCa patients. Conclusion: The data of this study demonstrated that the Gleason grade, tPSA, ALP, and TNM stage of PCa patients are independently correlated with PFS, and a nomogram model based on these indicators may be valuable for the PFS prediction in PCa patient.

Circular RNA hsa_circ_0075542 acts as a sponge for microRNA-1197 to suppress malignant characteristics and promote apoptosis in prostate cancer cells.

Numerous differentially expressed circular RNAs (circRNAs) have been identified; however, their roles have not been fully elucidated. Since dysregulated circRNAs may have clinical applications, it is vital to study their expression characteristics, function, and mechanism in prostate cancer cells. The role, regulatory mechanism, and expression of hsa_circ_0075542 were analyzed using quantitative reverse transcription polymerase chain reaction. The results indicated that the expression of hsa_circ_0075542 was downregulated in prostate tumor tissues. The functions of prostate cancer cell lines LNCaP and PC3 cells were assessed using cell counting kit-8 and transwell assays and flow cytometry analysis. The results of the functional experiments showed that overexpression of hsa_circ_0075542 suppressed cell proliferation, reduced migration and invasiveness capabilities, and promoted apoptosis. Moreover, hsa_circ_0075542 targeted the microRNA-1197 (miR-1197) homeobox C11 (HOXC11) axis by sponging miR-1197. Overexpression of miR-1197 played a tumor-promoting role. Overexpression of hsa_circ_0075542 alleviated the tumor-promoting effect of miR-1197 overexpression In conclusion, hsa_circ_0075542 suppressed malignant characteristics and promoted apoptosis in LNCaP and PC3 cells by acting as a competing endogenous RNA of miR-1197. The hsa_circ_0075542/miR-1197 axis might play a role via HOXC11.

HJURP promotes proliferation in prostate cancer cells through increasing CDKN1A degradation via the GSK3ß/JNK signaling pathway.

Genes with cross-cancer aberrations are most likely to be functional genes or potential therapeutic targets. Here, we found a total of 137 genes were ectopically expressed in eight cancer types, of which Holliday junction recognition protein (HJURP) was significantly upregulated in prostate cancer (PCa). Moreover, patients with higher HJURP mRNA and protein levels had poorer outcomes, and the protein levels served as an independent prognosis factor for the overall survival of PCa patients. Functionally, ectopic HJURP expression promoted PCa cells proliferation in vitro and in vivo. Mechanistically, HJURP increased the ubiquitination of cyclin-dependent kinase inhibitor 1 (CDKN1A) via the GSK3ß/JNK signaling pathway and decreased its stability. This study investigated the role of HJURP in PCa proliferation and may provide a novel prognostic and therapeutic target for PCa.

GTSE1 promotes prostate cancer cell proliferation via the SP1/FOXM1 signaling pathway.

G2 and S phase-expressed-1 (GTSE1) has been implicated in the pathogenesis of several malignant tumors. However, its specific role in prostate cancer (PCa) remains unclear. In this study, RNA-Seq data from patients with PCa and controls were downloaded from the FIREBROWSE database, and it was found that the GTSE1 mRNA level was significantly upregulated in PCa. Moreover, patients with higher GTSE1 mRNA levels had higher Gleason scores (P < 0.001), a more advanced pT stage (P = 0.011), and a more advanced pN stage (P = 0.006) as well as a shorter time to biochemical recurrence (P = 0.005). In addition, overexpression of GTSE1 could promote proliferation in LNCaP cells, whereas silencing GTSE1 could inhibit the growth of C4-2 cells in vitro and in vivo. Mechanistically, GTSE1 enhanced the expression of FOXM1 by upregulating the SP1 protein level, a transcription factor of FOXM1, which ultimately promoted PCa cell proliferation. In summary, GTSE1 is a new candidate oncogene in the development and progression of PCa, and it can promote PCa cell proliferation via the SP1/FOXM1 signaling pathway.

[Primary urothelial carcinoma of the prostate: A case report and review of the literature].

OBJECTIVE: To investigate the clinical diagnosis, treatment and prognosis of primary urothelial carcinoma of the prostate. METHODS: We retrospectively analyzed the clinical data on one case of primary urothelial carcinoma of the prostate and reviewed the relevant published literature. RESULTS: The patient, aged 83 years old and diagnosed with primary urothelial carcinoma of the prostate, was treated by neoadjuvant chemotherapy with gemcitabine plus cisplatin preoperatively, injected with 5-fluorouracil into the cutting edge of the tumor intraoperatively, and pathologically confirmed with high-grade invasive primary urothelial carcinoma of the prostate, followed by adjuvant chemotherapy with gemcitabine plus cisplatin. No recurrence or metastasis was observed during 1-year follow-up. CONCLUSIONS: Primary urothelial carcinoma of the prostate is rare and highly malignant. If the tumor is localized, the patient needs to be treated by neoadjuvant chemotherapy preoperatively, injection with anti-tumor drugs into the cutting edge of the tumor intraoperatively, and adjuvant chemotherapy and regular follow-up postoperatively.

[Comparison of the disposable circumcision stapler, disposable prepuce ligator and traditional surgical method in circumcision].

OBJECTIVE: To compare the effects and complications of the disposable circumcision stapler, disposable prepuce ligator and traditional surgical method in circumcision. METHODS: This retrospective study included 327 cases of phimosis or redundant prepuce treated by circumcision with the disposable circumcision stapler (the DCS group, n = 133), disposable prepuce ligator (the DPL group, n = 105) or traditional surgical method (the TS group, n = 89) in our hospital from June 2019 to June 2020. We compared the three surgical methods in terms of operation time, intraoperative blood loss, pain score, satisfaction of the patients with the penile appearance and incidence rates of incision edema, hematoma, infection and dehiscence. RESULTS: The DCS and DPL groups, compared with the TS group, showed significantly shorter operation time (ï¼»9.72 ± 2.17ï¼½ and ï¼»10.57 ± 2.31ï¼½ vs ï¼»36.13 ± 6.85ï¼½ min, P < 0.01), less intraoperative blood loss (ï¼»2.07 ± 0.96ï¼½ and ï¼»2.53 ± 1.46ï¼½ vs ï¼»14.33 ± 4.92ï¼½ ml, P < 0.01) and higher appearance satisfaction score (4.07 ± 0.80 and 3.93 ± 0.96 vs 3.13 ± 1.06, P < 0.05). The DCS and TS groups, in comparison with the DPL group, exhibited markedly lower pain score (1.87 ± 0.99 and 2.27 ± 1.16 vs 3.87 ± 1.30, P < 0.01) and the rates of postoperative incision hematoma (3.01% and 2.25% vs 9.52%, P < 0.05), and infection and dehiscence (2.45% and 2.04% vs 8.07%, P < 0.05). The postoperative rate of incision edema was remarkably lower in the DCS than in the DPL and CS groups (10.2% vs 20.2% and 23.5%, P < 0.05). CONCLUSIONS: Circumcision with the disposable circumcision stapler, with the advantages of simple operation, short operation time, less bleeding, less pain, satisfactory appearance, and lower incidence of complications, deserves clinical application and promotion.

MicroRNA-488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3.

Prostate cancer (PCa) remains the second leading cause of cancer-related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. By analyzing the Gene Expression Omnibus dataset, we found lower expression for miR-488 in PCa than in normal tissues. Moreover, CCK-8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR-488 in PCa cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis. In contrast, downregulation of miR-488 expression promoted proliferation and glycolysis in PCa cells. Using a bioinformatic approach and dual-luciferase reporter assays, we identified 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform3 (PFKFB3), as a direct target of miR-488. Inhibition of PFKFB3 also suppressed PCa cell glycolysis and proliferation. Our study suggests that miR-488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and thus, miR-488 may be a novel therapeutic candidate for PCa.

Hyperglycaemia-induced miR-301a promotes cell proliferation by repressing p21 and Smad4 in prostate cancer.

Hyperglycaemia promotes the development of Prostate cancer (PCa). However, the roles of miRNAs in this disease process and the underlying mechanisms are largely unknown. In this study, we recruited 391 PCa patients in China and found that PCa patients with high level blood glucose (≥100 mg/dL) trended to have high Gleason score (GS ≥ 7). miRNA-301a levels were significantly higher in prostate cancer than that in normal prostate tissues. Hyperglycaemia or high glucose treatment induced miR-301a expression in prostate tissues or PCa cell lines. miR-301a suppressed the expression of p21 and Smad4, and subsequently promoted G1/S cell cycle transition and cell proliferation in vitro and xenograft growth in nude mice in vivo. Furthermore, knockdown of p21 and Smad4 mimicked the effects of miR-301a overexpression. Restoration of p21 and smad4 could interrupt the effects of miR-301a overexpression. Importantly, inhibition of miR-301a severely blocked high glucose-induced PCa cell growth both in vitro and in vivo. These results revealed a novel molecular link between hyperglycaemia and PCa. The miR-301a plays an important role in the hyperglycaemia-associated cancer growth, and represents a novel therapeutic target for PCa.