A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1.

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.

Global, regional, and national burden of kidney, bladder, and prostate cancers and their attributable risk factors, 1990-2019.

BACKGROUND: The burden of kidney, bladder, and prostate cancers has changed in recent decades. This study aims to investigate the global and regional burden of, and attributable risk factors for genitourinary cancers during the past 30 years. METHODS: We extracted data of kidney, bladder, and prostate cancers from the Global Burden of Disease 2019 database, including incidence, mortality, disability-adjusted life-years (DALYs), and attributable risk factors from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age-standardized incidence rate, age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). The associations between cancers burden and socio-demographic index (SDI) were also analyzed. RESULTS: Compared with 1990, the global incident cases in 2019 were higher by 154.78%, 123.34%, and 169.11% for kidney, bladder, and prostate cancers, respectively. During the 30-year study period, there was a downward trend in ASMR and ASDR for bladder cancer (EAPC = - 0.68 and - 0.83, respectively) and prostate cancer (EAPC = - 0.75 and - 0.71, respectively), but an upward trend for kidney cancer (EAPC = 0.35 and 0.12, respectively). Regions and countries with higher SDI had higher incidence, mortality, and DALYs for all three types of cancers. The burden of bladder and prostate cancers was mainly distributed among older men, whereas the burden of kidney cancer increased among middle-aged men. Smoking related mortality and DALYs decreased, but high body mass index (BMI) and high fasting plasma glucose (FPG) related mortality and DALYs increased among kidney, bladder, and prostate cancers during the study period. CONCLUSIONS: Kidney, bladder, and prostate cancers remain major global public health challenges, but with distinct trend for different disease entity across different regions and socioeconomic status. More proactive intervention strategies, at both the administrative and academic levels, based on the dynamic changes, are needed.

[Modified Brisson surgery combined with skin flap clipping for the treatment of severe concealed penis in children].

OBJECTIVE: To explore the effect of modified Brisson surgery combined with the skin flap clipping technique in the treatment of severe concealed penis in children. METHODS: We retrospectively analyzed the clinical data on 165 children with severely concealed penis treated in our hospital from January 2014 to January 2019, 105 by modified Brisson surgery combined with the skin flap clipping technique and the other 60 by modified Devine surgery, all the operations performed by the same surgeon. We compared the two surgical strategies concerning operation time, intraoperative blood loss, postoperative increase of penile exposure, preputial edema duration, flap necrosis and penile retraction, and satisfaction of the patients' parents with the overall surgical effect. RESULTS: No injury of the dorsal nerve or urethra, nor postoperative refractory prepuce edema or painful erection was found in any of the cases. The patients treated by modified Brisson surgery, in comparison with those treated by modified Devine surgery, showed significantly less intraoperative blood loss (ï¼»8.4 ± 1.60ï¼½ vs ï¼»12.6 ± 2.10ï¼½ ml, P < 0.05), more postoperative increase of penile exposure (ï¼»2.7 ± 0.29ï¼½ vs ï¼»2.3 ± 0.22ï¼½ cm, P < 0.05), fewer cases of flap necrosis (1 vs 4, P < 0.05) and higher rate of satisfaction with the overall surgical effect (94.9% vs 84.5%, P < 0.05), but there were no statistically significant differences between the former and the latter groups in the operation time (ï¼»48.3 ± 4.1ï¼½ vs ï¼»48.1 ± 5.0ï¼½ min, P > 0.05) or the postoperative duration of prepuce edema (ï¼»3.3 ± 0.93ï¼½ vs ï¼»3.2 ± 0.90ï¼½ d, P > 0.05) or number of cases of penile retraction at 6 months (1 vs 1, P > 0.05). CONCLUSIONS: Modified Brisson surgery combined with the skin flap clipping technique can achieve satisfactory results in the treatment of severe concealed penis in children and therefore deserves to be popularized in clinical application.

Prognostic value of perioperative leukocyte count in resectable gastric cancer.

AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer. METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors. RESULTS: The mean white blood cell count (WBC) significantly decreased after surgery, and 107/614 (17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 10(9)/L and postoperative WBC < 4.0 × 10(9)/L, with an absolute decrease ≥ 0.5 × 10(9)/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio (HR) = 1.602, 95% confidence interval (CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, pTNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p-leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia (27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer.