Purpose. KIF20A is essential in the process of spindle assembly and cytokinesis regulation. The role of KIF20A during tumorigenesis and tumor development has been well studied in several cancers. But the association between the KIF20A clinical role and prostate cancer (PCa) has not been reported yet. In this study, we investigated its potential prognostic effect and its role in progression of prostate cancer. Methods. Real-time quantitative polymerase chain reaction and Western blots were used to investigate the KIF20A transcription and translation levels in 7 pairs of fresh PCa tissue and adjacent normal prostate tissue. Immunohistochemistry (IHC) was used to investigate the KIF20A protein level in 114 PCa tissue samples. Bioinformatics analysis was performed to analyze the effect of KIF20A in oncologic prognosis in PCa patients. MTT assay, transwell assay, and colony formation assay in vitro and tumor formation assay in vivo were performed to evaluate the biological behavior of KIF20A in prostate cancer. Results. KIF20A was significantly elevated in tumor tissue compared with normal prostate tissue at both the mRNA and the protein level. High expression of KIF20A at the protein level was correlated with adverse clinicopathological features. Bioinformatics analysis showed that the high KIF20A expression group has a poor biochemical recurrence- (BCR-) free survival. Knocking down KIF20A suppressed the proliferation, migration, and invasion of the prostate cancer cell both in vitro and in vivo. Conclusions. Our data demonstrated that the high expression of KIF20A was associated with poor clinical outcome and targeting KIF20A could reduce proliferation, migration, and invasion of the prostate cancer cell, indicating that KIF20A might be a potential prognostic and therapeutic target for PCa patients.

Background: This study aims to present the trends of incidence and mortality of kidney cancer from 1990 to 2016 by age, gender, geographical region, regional, and sociodemographic index (SDI), and then forecast the future trends to 2030. Methods: Data of this study were gathered from the Global Burden of Disease Study (GBD), including 195 countries and territories, accounting for 21 regions. Over-time trends from 1990 to 2016 were analyzed by gender, geographical region, age range and SDI. Based on the big data, we forecasted the future trends to 2030 by ARIMA model. All the data were analyzed by R software (x64 version 3.5.1), SAS (version 9.3) and SPSS (version 22.0). Results: Globally, in 2016, there were 342,100 [95% uncertainty interval (UI), 330,759–349,934] incident cases of kidney cancer and the number of deaths were 131,800 (127,335–136,185). The age-standardized incidence rate (ASIR) and death rate (ASDR) were 4.97 (4.81–5.09) per 100,000 and 2.00 (1.93–2.06) per 100,000, respectively. Globally, the estimated risk of kidney cancer for male within the age of 30 and 70 is around 0.79% compared to 0.41% for female. In other words, the probability of developing kidney cancer was generally higher in male than in female. By 2030, incidence of kidney cancer in both sexes are projected to increase substantially in high SDI, followed by middle SDI, low-middle SDI, and low SDI countries. High SDI and low SDI countries will also have increased mortality rates of kidney cancers. Globally, the trends in deaths due to kidney cancer will remain stable. Conclusions: The incidence and death rate of kidney cancer are highly variable among SDI countries and regions but have increased uniformly from 1990 to 2016. By 2030, the future incidence of kidney cancer will grow continuously especially in high SDI countries, middle SDI, low-middle SDI, and low SDI countries.

Background: This study aims to explore and project the temporal trends in incidence and mortality of testicular cancer. Moreover, it can provide theoretical guidance for the rational allocation of health resources. Methods: This study analyzed existing data on testicular cancer morbidity and mortality from 1990 to 2016 and predicted time-varying trends of age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) from 2017 to 2030 in different ages, regions and sociodemographic index (SDI) quintile sub-groups. Result: Globally, numbers of testicular cancer cases in 2016 [66,833; 95% uncertainty interval (UI), 64,487–69,736] are 1.8 times larger than in 1990 (37,231; 95% UI, 36,116–38,515). The testicular cancer-related death cases increased slightly from 8,394 (95% UI, 7,980–8,904) in 1990 to 8,651 (95% UI, 8,292–9,027) in 2016. In aspect of ASIR, the data showed an up-trend from 0.74 (95% UI, 0.72–0.77) in 1990 to 0.88 (95% UI, 0.85–0.92) in 2016. The ASDR of testicular cancer declined from 0.18 (95% UI, 0.17–0.19) in 1990 to 0.12 (95% UI, 0.11–0.12) in 2016. From 2017 to 2030, predictions of trends in testicular cancer indicate that the ASIRs of most SDI countries are rising, but the ASDRs trends in testicular cancer will decrease. Conclusions: By analyzing the available and reliable data in different ages, regions and SDI, this study shows a significant upward trend in incidence and a slow upward trend in mortality of testicular cancer from 1990 to 2016, and simultaneously, predicts the increase of ASIR and the downward trend of ASDR in 2017–2030.

Background: Previous study has reported that loss of epithelial androgen receptor (AR) may promote tumor progression and cause TRAMP mouse model die earlier. The detail mechanisms, however, remain unclear. Methods: Immunohistochemistry assay, Western blot and real-time PCR were used to detect the expression of epithelial and mesenchymal markers. RNA extraction, RT-PCR, quantitative RT-PCR, BrdU incorporation assays, flow cytometry and other experimental technics were also used in present work. Results: Decreased expression of epithelial markers (Cytokeratin 8, NKX3.1 and E-cadherin) and increased expression of mesenchymal markers (α-SMA, Vimentin, and N-cadherin) in were found in AR knockout TRAMP tumors. Further investigation indicated that AR signal deprivation is associated with cell morphology transition, high cell mobility, high cell invasion rate and resistance to anoikis in TRAMP prostate tumor cells. Together, these findings implied knockout AR in TRAMP prostate tumor may lead to EMT, which may result in earlier metastasis, and then cause TRAMP mice die earlier. TGF-β1 is responsible for EMT in AR knockout TRAMP tumor cells. Conclusions: In conclusion, ADT therapy induced hormone refractory prostate cancer may gain the ability of metastasis through cell’s EMT which is a phase of poor differentiation. Anti-EMT drugs should be developed to battle the tumor metastasis induced by ADT therapy.

The FDA-approved anti-androgen Enzalutamide (Enz) has been used successfully as the last line therapy to extend castration-resistant prostate cancer (CRPC) patients’ survival by an extra 4.8 months. However, CRPC patients eventually develop Enz-resistance that may involve the induction of the androgen receptor (AR) splicing variant ARv7. Here we found that Cisplatin (Cis) or Carboplatin, currently used in chemotherapy/radiation therapy to suppress tumor progression, could restore the Enz sensitivity in multiple Enz-resistant (EnzR) CRPC cells via directly degrading/suppressing the ARv7. Combining Cis or Carboplatin with Enz therapy can also delay the development of Enz-resistance in CRPC C4-2 cells. Mechanism dissection found that Cis or Carboplatin might decrease the ARv7 expression via multiple mechanisms including targeting the lncRNA-Malat1/SF2 RNA splicing complex and increasing ARv7 degradation via altering ubiquitination. Preclinical studies using in vivo mouse model with implanted EnzR1-C4-2 cells also demonstrated that Cis plus Enz therapy resulted in better suppression of EnzR CRPC progression than Enz treatment alone. These results not only unveil the previously unrecognized Cis mechanism to degrade ARv7 via targeting the Malat1/SF2 complex and ubiquitination signals, it may also provide a novel and ready therapy to further suppress the EnzR CRPC progression in the near future.