Diagnosis and treatment of primary seminoma of the prostate:A case report and review of literature

BACKGROUND Primary seminoma of the prostate(PSP)is a rare type of extragonadal germ cell tumour that is easily misdiagnosed,owing to the lack of specific clinical features.It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis.CASE SUMMARY A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital.A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy.Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles.Further radiotherapy treatment for the local lesion was performed,and the patient had a disease-free survival period of 96 mo.This case was analysed along with 13 other cases of PSP identified from the literature.Only four of the cases(28.6%)were initially confirmed by prostate biopsy.In these cases,imaging examinations showed an enlarged prostate(range 6-11 cm)involving the bladder neck(13/14).Of the 14 total cases,11(78.6%)presented typical pure seminoma cell features,staining strongly positive for placental alkaline phosphatase,CD117,and OCT4.The median age at diagnosis was 51(range 27-59)years,and patients had a median progression-free survival time of 48(range 6-156)mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy.The remaining three were cases of mixed embryonal tumours with focal seminoma,which had clinical features similar to those of pure PSP,in addition that they also had elevated serum alpha fetoprotein,beta-human chorionic gonadotropin,and lactose dehydrogenase.CONCLUSION PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck.Further prostate biopsies may aid in proper PSP diagnosis.Cisplatin-based chemotherapy is still the main primary therapy for PSP.

Cognitive magnetic resonance imaging-ultrasound fusion transperineal targeted biopsy combined with randomized biopsy in detection of prostate cancer

BACKGROUND Prostate cancer(PCa)is one of the most common cancers among men.Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging(mp-MRI)have emerged,which may improve the accuracy of detecting clinically significant PCa in recent years.AIM To investigate the diagnostic efficiency of a template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa.METHODS Data from patients with an increasing prostate-specific antigen(PSA)level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed.All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area.A total of 127 patients with complete data were included in the final analysis.A multivariable logistic regression analysis was conducted,and a two-sided P<0.05 was considered statistically significant.RESULTS PCa was detected in 66 of 127 patients,and 56 cases presented clinically significant PCa.Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa,specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa.A randomized biopsy detected seven cases of PCa negative on targeted biopsy,and four cases had clinically significant PCa.PSA density(OR:1.008,95%CI:1.003-1.012,P=0.001;OR:1.006,95%CI:1.002-1.010,P=0.004)and Prostate Imaging-Reporting and Data System(PI-RADS)scores(both P<0.001)were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone.CONCLUSION This single-centered study proposed a feasible template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy.Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.

^(68)Ga-PSMA PET/CT versus CT and bone scan for investigation of PSA failure post radical prostatectomy

Objective:To evaluate the use of Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography(^(68)Ga-PSMA PET/CT),compared with conventional CT abdomen/pelvis(CTAP)and whole body single photon emission CT bone scan(BS),for detection of local or distant metastasis following biochemical failure/recurrence in post-prostatectomy patients.Methods:We conducted a review of our prospectively maintained,institutional database to identify 384 patients with post-prostatectomy biochemical failure/recurrence who underwent PSMA PET/CT,CTAP and BS from February 2015 to August 2017 in Nepean Hospital,tertiary referral centre.The results of the three imaging modalities were analysed for their ability to detect local recurrence and distant metastases.PSMA PET/CT and CTAP imaging were separately performed on the same day and the BS was performed within several days(mostly in 24 h).Difference in detection rates was determined between the modalities and the Chi square test was used to determine significance.Results:A total of 384 patients were identified with a median prostate-specific antigen(PSA)of 0.465 ng/mL(interquartile range =0.19-2.00 ng/mL).Overall,PSMA PET/CT was positive for 245(63.8%)patients whereas CTAP and BS were positive in 174 patients(45.3%).A total of 98 patients(25.5%)had local or distant metastasis detected on PSMA only,while 20 patients(5.2%)had recurrences detected on CTAP but not on PSMA PET/CT.Conclusion:The use of PSMA PET/CT has a higher detection rate of predicted local or distant metastasis compared to CTAP and BS in the staging of patients with biochemical recurrences after radical prostatectomy.

Impact of tertiary Gleason pattern 5 on prostate cancer aggressiveness:Lessons from a contemporary single institution radical prostatectomy series

Objective:To better evaluate tertiary Gleason pattern reporting and to evaluate the impact of tertiary Gleason pattern 5(TP5)on prostate cancer pathological features and biochemical recurrence at our large single institution.Methods:We retrospectively reviewed 1962 patients who underwent radical prostatectomy(RP)for prostate cancer;TP5 was reported in 159 cases(8.1%).Men with Gleason score(GS)7 and GS 8 disease were divided into subgroups with and without TP5,and histopathological features were compared.Multivariate analyses were conducted to assess the impact on TP5 on biochemical-free survival(BFS).Results:Tumors possessing GS 3+4 with TP5 were more likely to exhibit extraprostatic extension(EPE)and had a larger tumor diameter(TD)than GS 3+4 alone.GS 3+4 with TP5 was also associated with positive surgical margins(SM),seminal vesicle involvement(SVI),and higher pre-operative prostate-specific antigen(PSA)values,but without statistical significance.GS 4+3 with TP5 more commonly presented with EPE,positive SM,SVI,and greater TD and pre-operative PSA level than GS 4+3 alone.In multivariate analysis,Gleason score,EPE,and TP5 were overall independent risk factors for PSA recurrence in this cohort.Additionally,GS 4+3 with TP5 was associated with shorter time to recurrence versus GS 4+3 alone.Conclusion:Our results emphasize the importance of TP5 and suggest that criteria for tertiary pattern reporting in prostate cancer should be standardized.Further studies are needed to evaluate the role of tertiary patterns in prognostic models.

Biochemical recurrence of pathological T2+localized prostate cancer after robotic-assisted radical prostatectomy:A 10-year surveillance

BACKGROUND pT2+prostate cancer(PCa),a term first used in 2004,refers to organ-confined PCa characterized by a positive surgical margin(PSM)without extracapsular extension.Patients with a PSM are vulnerable to biochemical recurrence(BCR)following radical prostatectomy(RP);however,whether adjuvant radiotherapy(aRT)is imperative to PSM after RP remains controversial.This study had the longest follow-up on pT2+PCa after robotic-assisted RP since 2004.Moreover,we discussed our viewpoints on pT2+PCa based on real-world experiences.AIM To conclude a 10-year surveillance on pT2+PCa and compare our results with those of the published literature.METHODS Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled.Two serial tests of prostate specific antigen(PSA)≥0.2 ng/mL were defined as BCR.Various designed factors were analyzed using statistical tools for BCR risk.SAS 9.4 was applied and significance was defined as P<0.05.Univariate,multivariate,linear regression,and receiver operating characteristic(ROC)curve analyses were performed for statistical analyses.RESULTS With a median follow-up period of 9 years,25(52%)patients had BCR(BCR group),and the remaining 23(48%)patients did not(non-BCR group).The median time for BCR test was 4 years from the first postoperative PSA nadir.Preoperative PSA was significantly different between the BCR and non-BCR groups(P<0.001),and ROC curve analysis of preoperative PSA suggested a cutoff value of 19.09 ng/mL(sensitivity,0.600;specificity:0.739).The linear regression analysis showed no correlation between time to BCR and preoperative PSA(Pearson’s correlation,0.13;adjusted R2=0.026).CONCLUSION Robotic-assisted RP in pT2+PCa of worse conditions can provide better BCR-free survival.A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+PCa BCR rate.Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR.Based on our experiences and review of the literature,we do not recommend routine aRT for pT2+PCa.

Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer:A meta-analysis and systematic review

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases.Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model.Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Oral microbiota in the oral-genitourinary axis:identifying periodontitis as a potential risk of genitourinary cancers

Periodontitis has been proposed as a novel risk factor of genitourinary cancers:although periodontitis and genitourinary cancers are two totally distinct types of disorders,epidemiological and clinical studies,have established associations between them.Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis.Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers.Therefore,oral microbiota provides the bridge between periodontitis and genitourinary cancers.We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers.We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer,and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial

Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.

Indications,strategies,and development on prostate targeted biopsy:Report of the Panjiayuan Consensus Conference 2022

Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supported by high-quality evidence.However,the TB indications and strategies are controversial.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,invited a panel of recognized urology experts in PCa to address these topics at the Panjiayuan Consensus Conference 2022.The conference results on prostate TB are presented herein.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences identified 10 key areas of prostate biopsy:(1)selection of imaging examination;(2)indications of TB;(3)transperineal and transrectal prostate biopsy;(4)TB pathways;(5)TB and SB;(6)three techniques of TB;(7)the number of TB cores needed for one lesion;(8)core number for SB;(9)free-hand TB;(10)future development of TB/prostate diagnosis.Thus,a panel of 25 recognized urologists and 2 radiologists from China were invited to attend this conference.The panel voted anonymously on 14 predetermined questions.Voting was based on the panelists'clinical practice and opinion,rather than high-level evidence.The voting outcomes were supported by the panel unequally,and details of the voting results were reported.The voting results can help clinicians to decide on biopsy timing and proper strategies,for which guidelines are sparse.We also focused on the future development of TB and SB,such as the combined pathway of TB and SB,techniques of TB,biopsy cores,free-hand TB,and prostate-specific membrane antigen positron emission tomography/computed tomography.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia:a subgroup analysis of the TITAN trial

Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer(mCSPC).The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial was conducted at 260 sites in 23 countries.This subgroup analysis included patients enrolled in 62 participating centers in China,Japan,and Korea.Radiographic progression-free survival(PFS),time to prostate-specific antigen(PSA)progression,and PSA changes from baseline were compared between groups in the East Asian population.The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups,respectively.The 24-month radiographic PFS rates were 76.1%and 52.3%in the apalutamide and placebo groups,respectively(apalutamide vs placebo:hazard ratio[HR]=0.506;95%confidence interval[CI],0.302–0.849;P=0.009).Median time to PSA progression was more favorable with apalutamide than placebo(HR=0.210;95%CI,0.124–0.357;P<0.001).Median maximum percentages of PSA decline from baseline were 99.0%and 73.9%in the apalutamide and placebo groups,respectively.The most common adverse event(AE)was rash in the apalutamide group,with a higher rate than that in the placebo group(37.3%vs 9.1%).The most common grade 3 or 4 AEs were rash(12[10.9%])and hypertension(12[10.9%])for apalutamide.The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Erectile function after WSTll vascular-targeted photodynamic therapy for low-risk prostate cancer treatment

Vascular-targeted photodynamic therapy(VTP)using padeliporfin is currently assessed as a low-risk prostate cancer(LRPCa)treatment.The aim of this study was to assess erectile function outcomes of VTP for LRPCa treatment.We prospectively included all patients treated with VTP for LRPCa.The primary endpoint was the post-treatment International Index of Erectile Function score(IIEF5 score)evolution(at 6 months,12 months,and then every year for 5 years).Secondary endpoints were the need of erectile dysfunction(ED)treatment and its efficacy.Eighty-two men were included.The median follow-up was 68(range:6-89)months.There was a 3-point significant decrease in the median IIEF5 score between baseline and at 6 months post-VTP(23[range:1-25]vs 20[range:1-25],P=0.005).There was a 1-point decrease at 1 year and 2 years post-VTP compared to baseline(22[range:2-25]and 22[range:0-25],P<0.005).There was no significant difference at 3,4,and 5 years compared to baseline.Twenty-seven(32.9%)patients received ED treatment:phosphodiesterase type-5 inhibitors(PDEI5;n=18),intracavernous injections(ICI;n=9),and intra-urethral gel(n=1).The median IIEF5 score statistically significantly increased after ED treatment(7[range:0-24]vs 21[range:1-25],P<0.001).ED treatment was efficient for 75%of the patients.There was no statistically significant difference between IIEF5 score at baseline and after ED treatment(P=0.443).Forty-six patients were totally potent before VTP and among them,13 needed ED treatment post-VTP with a success rate of 69.2%.VTP induced minimal changes in erectile function with a 3-point and a 1-point reduction in the IIEF5 score at 6 months and at 1 year,respectively.When required,ED treatment was efficient.

Complete androgen blockade vs.medical castration alone as adjuvant androgen deprivation therapy for prostate cancer patients following radical prostatectomy:a retrospective cohort study

Background:Till date,the optimal treatment strategy for delivering adjuvant androgen deprivation therapy(ADT)in localized and locally advanced prostate cancer(PCa),as a lower stage in PCa progression compared with metastatic PCa,is still unclear.This study compares the efficacy of castration alone with complete androgen blockade(CAB)as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy(RP).Methods:Patients diagnosed with PCa,without lymph node or distant metastasis,who received RP in West China Hospital between January 2009 and April 2019,were enrolled in this study.We performed survival,multivariable Cox proportional hazard regression,and subgroup analyses.Results:A total of 262 patients were enrolled,including 107 patients who received castration alone and 155 patients who received CAB.The survival analysis revealed that there was no significant difference between the two groups(hazard ratios[HR]=1.07,95%confidence intervals[95%CI]=0.60-1.90,P=0.8195).Moreover,the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant.Similarly,there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models.Furthermore,our subgroup analysis showed that CAB achieved better biochemical recurrence(BCR)outcomes than medical castration alone as adjuvant ADT for locally advanced PCa(P for interaction=0.0247,HR=0.37,95%CI=0.14-1.00,P=0.0497).Conclusion:Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

The role of radical prostatectomy and definitive external beam radiotherapy in combined treatment for high-risk prostate cancer:a systematic review and meta-analysis

The first-line treatment options for high-risk prostate cancer(PCa)are definitive external beam radiotherapy(EBRT)with or without androgen deprivation therapy(ADT)and radical prostatectomy(RP)with or without adjuvant therapies.However,few randomized trials have compared the survival outcomes of these two treatments.To systematically evaluate the survival outcomes of high-risk PCa patients treated with EBRT-or RP-based therapy,a comprehensive and up-to-date meta-analysis was performed.A systematic online search was conducted for randomized or observational studies that investigated biochemical relapse-free survival(bRFS),cancer-specific survival(CSS),and/or overall survival(OS),in relation to the use of RP or EBRT in patients with high-risk PCa.The summary hazard ratios(HRs)were estimated under the random effects models.We identified heterogeneity between studies using Q tests and measured it using I2 statistics.We evaluated publication bias using funnel plots and Egger's regression asymmetry tests.Seventeen studies(including one randomized controlled trial[RCT])of low risk of bias were selected and up to 9504 patients were pooled.When comparing EBRT-based treatment with RP-based treatment,the pooled HRs for bRFS,CSS,and OS were 0.40(95%confidence interval[CI]:0.24–0.67),1.36(95%CI:0.94–1.97),and 1.39(95%CI:1.18–1.62),respectively.Better OS for RP-based treatment and better bRFS for EBRT-based treatment have been identified,and there was no significant difference in CSS between the two treatments.RP-based treatment is recommended for high-risk PCa patients who value long-term survival,and EBRT-based treatment might be a promising alternative for elderly patients.

Peripheral zone PSA density:a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml^(-1)

To improve the diagnostic efficiency of prostate cancer(PCa)and reduce unnecessary biopsies,we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen(PSA)density(PZ-PSAD).Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital(Shanghai,China)between January 2012 and January 2018 were retrospectively identified(n=529).Another group of patients with benign prostatic hyperplasia(n=100)were randomly preselected to obtain the PSA density of the non-PCa cohort(N-PSAD).Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging(mpMRI)and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm.Receiver operating characteristic(ROC)curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level,and the area under the ROC curve(AUC)of PZ-PSAD was higher than that of PSA,PSA density(PSAD),and transition zone PSA density(TZ-PSAD).PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography(TRUS)and mpMRI results.When TRUS and mpMRI findings were ambiguous to predict PCa(PIRADS score≤3),PZ-PSAD could increase the positive rate of biopsy from 21.7%to 54.7%,and help 63.8%(150/235)of patients avoid unnecessary prostate biopsy.In patients whose PSA was 4.0–10.0 ng ml^(−1),10.1–20.0 ng ml^(−1),and>20.0 ng ml^(−1),the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml^(−2),0.297 ng ml^(−2),and 1.180 ng ml^(−2),respectively(sensitivity>90%).Compared with PSA,PSAD,and TZ-PSAD,the efficiency of PZ-PSAD for predicting PCa is the highest,leading to fewer missed diagnoses and unnecessary biopsies.

Upregulation of erythropoietin and erythropoietin receptor in castration-resistant progression of prostate cancer

Hypoxia-induced erythropoietin signaling plays an important role in tumor growth and invasion.In the present study,we investigated the contribution of erythropoietin signaling pathway to castration-resistant prostate cancer and the development of a neuroendocrine phenotype.Immunohistochemical staining showed that the erythropoietin and erythropoietin receptor scores in castration-resistant prostate cancer and androgen-dependent prostate cancer were 7.55 versus 4.5 and 7.45 versus 5.9,respectively(P<0.001).Furthermore,a cell proliferation assay was conducted,and the differential expression of erythropoietin and erythropoietin receptor in LNCaP cells and hypoxia-induced LNCaP cells was evaluated using western blot and quantitative real-time PCR.The proliferation capacity of hypoxia-induced LNCaP cells was similar in cultures of both fetal bovine serum and charcoal-stripped fetal bovine serum,suggesting that LNCaP cells acquired hypoxia-induced androgen-independent growth.After 2 weeks of hypoxic culture,LNCaP cells showed a neuroendocrine cell change and increased expression of neuron-specific enolase,erythropoietin,and erythropoietin receptor;knockdown of erythropoietin receptor reversed the hypoxia-induced upregulation of neuron-specific enolase in the LNCaP cells.In conclusion,the concurrent upregulation of erythropoietin and erythropoietin receptor in castration-resistant prostate cancer suggests that the erythropoietin/erythropoietin receptor autocrine loop plays an important role in the progression of castration resistance and is responsible for the development of a neuroendocrine phenotype.

Long non-coding RNA small nucleolar RNA host gene 6 aggravates pancreatic cancer through upregulation of far upstream element binding protein 1 by sponging microRNA-26a-5p

Background:Pancreatic cancer(PC)is a highly deadly malignancy with few effective therapies.We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6(SNHG6)plays in PC cells by targeting far upstream element binding protein 1(FUBP1)via microRNA-26a-5p(miR-26a-5p).Methods::SNHG6 expression was predicted by bioinformatics,followed by verification via reverse transcription quantitative polymerase chain reaction.Then,the interactions among SNHG6,miR-26a-5p,and FUBP1 were detected through online software analysis,dual luciferase reporter assay and RNA pull-down.After that,cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6,miR-26a-5p,and FUBP1 and their roles in PC cells.Finally,the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice.A t-test,one-way and two-way analysis of variance were used for data analysis.Results::Compared with that in normal tissues,SNHG6 was highly expressed in PC tissues(1.00±0.05 vs.1.56±0.06,t=16.03,P<0.001).Compared with that in human pancreatic duct epithelial cells(HPDE6-C7),SNHG6 showed the highest expression in PANC-1 cells(1.00±0.06 vs.3.87±0.13,t=34.72,P<0.001)and the lowest expression in human pancreatic cancer cells(MIAPaCa-2)(1.00±0.06 vs.1.41±0.07,t=7.70,P=0.0015).Compared with the levels in the si-negative control group,SNHG6(0.97±0.05 vs.0.21±0.06,t=16.85,P<0.001),N-cadherin(0.74±0.05 vs.0.41±0.04,t=8.93,P<0.001),Vimentin(0.55±0.04 vs.0.25±0.03,t=10.39,P<0.001),andβ-catenin(0.62±0.05 vs.0.32±0.03,t=8.91,P<0.001)were decreased,while E-cadherin(0.65±0.06 vs.1.36±0.07,t=13.34,P<0.001)was increased after SNHG6 knockdown or miR-26a-5p overexpression,accompanied by inhibited cell proliferation,migration,and invasion.SNHG6 overexpression exerted the opposite effects.SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p.Silencing SNHG6 blocked the growth of PC in vivo.Conclusion::Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p,thus providing further supporting evidence for its use in PC treatment.