Chinese Prostate Cancer Patients Research Articles

PSCA rs1045531 Polymorphism and the Risk of Prostate Cancer in a Chinese Population Undergoing Prostate Biopsy.

Background and Purpose:This study explored the association between a single-nucleotide polymorphism of prostate stem cell antigen and prostate cancer in Chinese patients undergoing prostate biopsy.Materials and Methods:DNA from 416 patients undergoing prostate biopsy was typed for the prostate stem cell antigen rs1045531 single-nucleotide polymorphism. The frequency of the rs1045531 polymorphism in patients with prostate cancer and in patients with benign prostatic hyperplasia was compared. Associations between the polymorphism and the risk of prostate cancer, prostate special antigen, Gleason score, and clinical stage were analyzed.Results:Statistically significant differences in the distribution of the rs1045531 genotypes and alleles were found between prostate cancer and benign prostatic hyperplasia in patients undergoing prostate biopsy (P = .035 and .046, respectively). We found that the rs1045531 AC genotype was significantly associated with a high risk of prostate cancer in the heterozygote model (AC vs CC; odds ratio = 2.383, 95% confidence interval: 1.198-4.741, χ2 = 6.229, P = .013) and the dominant model (AA/AC vs CC; odds ratio = 2.169, 95% confidence interval: 1.112-4.229, χ2 = 5.228, P = .022). However, susceptibility of prostate cancer was decreased in the homozygote model (AA vs CC; odds ratio = 0.828, 95% confidence interval: 0.143-4.805, P = .601). When considering clinical factors, the rs1045531 showed an association with prostate special antigen of 10 ng/mL or greater, a Gleason score of 7 or greater, and a size of T2 or greater.Conclusion:Men with the rs1045531 AC genotype of prostate stem cell antigen were at higher risk of prostate cancer in Chinese patients undergoing prostate biopsy.

Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression

BackgroundGlobal disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. ObjectiveTo systematically explore the genomic complexity and define disease-driven genetic alterations in PCa. Design, setting, and participantsThe study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. Outcome measurements and statistical analysisThe genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses. Results and limitationsWe demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated. ConclusionsThere are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression. Patient summaryWe reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment.

Interleukin-35 as a predictor of prostate cancer in patients undergoing initial prostate biopsy.

BackgroundInterleukin (IL)-35 is a novel inhibitory cytokine and has recently been implicated in tumor immunity. However, the role of IL-35 in prostate cancer (PCa) has not been elucidated.ObjectiveTo evaluate the role of plasma IL-35 in the diagnosis and prognosis of PCa in Chinese patients undergoing initial prostate biopsy.Materials and methodsUsing ELISA, plasma IL-35 levels were measured in 180 patients, who underwent a prostate biopsy. The clinical correlation of IL-35 with clinicopathological parameters was also evaluated. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) curve analysis were performed to establish the role of IL-35 as a clinical biomarker.ResultsSeventy-five (41.6%) of patients were histopathologically confirmed to have PCa. Plasma IL-35 levels were significantly higher in PCa patients (134.48±78.48 pg/mL) compared to non-PCa patients (67.22±24.08 pg/mL). ROC analysis showed that IL-35 was an independent predictor of PCa. Furthermore, IL-35 was found to be a significantly independent predictor of PCa in a group of patients with prostate-specific antigen levels between 4 and 10 ng/mL; was also able to predict advanced PCa from localized PCa and bone metastasis positive PCa from negative PCa.ConclusionOur data suggest for the first time that plasma IL-35 levels are correlated with PCa and is the independent predictor of PCa progression and metastasis. Thus, IL-35 could be utilized as a potential biomarker for diagnosis and prognosis of PCa, could also aid in decision making and predict the stage of the disease.

Assessing cancer-specific anxiety in Chinese men with prostate cancer: psychometric evaluation of the Chinese version of the Memorial Anxiety Scale for Prostate Cancer (MAX-PC).

The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) was developed to identify and assess cancer-specific anxiety among men with prostate cancer (PCa); however, there is no Chinese version. The aim of our study was to translate the English version of MAX-PC into Chinese and evaluate the psychometric properties of it. The study cohort comprised 254 participants. Internal consistency including the Cronbach's alpha coefficient and item-total correlations were used to measure the reliability of the scale. Factor structure was analyzed by exploratory factor analysis and concurrent validity by comparing MAX-PC scores with anxiety subscale scores of the Hospital Anxiety and Depression Scale (HADS). Divergent validity was assessed by correlating MAX-PC with HADS depression subscale, while discriminant ability by comparing differences in MAX-PC scores between different patient groups. The Chinese version of MAX-PC demonstrated good reliability; the Cronbach's alpha coefficient for the total and three subscales (prostate cancer anxiety, PSA anxiety, and fear of recurrence) being 0.94, 0.93, 0.82, and 0.85, respectively. Exploratory factor analysis supported the three-factor structure of the scale established in the original version. Despite the somewhat underperformed divergent validity, the scale demonstrated good concurrent validity with a strong correlation with the HADS anxiety subscale (r=0.71, p<0.01). Moreover, discriminant ability was demonstrated by ability to differentiate between disease stages. The MAX-PC Chinese version was confirmed to be a valid, reliable instrument and is thus appropriate for identifying and quantifying cancer-specific anxiety in Chinese PCa patients.

Single-nucleotide polymorphism rs1058205 of KLK3 is associated with the risk of prostate cancer: A case-control study of Han Chinese men in Northeast China.

BackgroundProstate cancer (PCa) is a serious public health concern for men worldwide. However, the risk factors for PCa remain largely unclear. Aim of this study was to investigate statistical associations between the risk of prostate cancer and the rs1058205 single-nucleotide polymorphism (SNP) of the KLK3 gene, which encodes the prostate specific antigen (PSA), in a case-control study of Han Chinese men in Northeast China.MethodsUsing a high-resolution melting curve genotyping method, we determined the genotype and allele distributions of rs1058205 in 2 groups of Han Chinese men, consisting of 268 PCa patients and 298 healthy control subjects. Logistic regression was used to evaluate associations between rs1058205 genotypes and the risk of PCa. Tumor staging and Gleason score were included in a stratified analysis of PCa risk.ResultsThe frequency of the TC genotype of rs1058205 in the PCa group was significantly lower than that in the control group (P = 0.049). The serum PSA level in participants with the TC genotype was significantly lower than that of the TT and CC genotypes in both the PCa and control groups (P < 0.010 for both). The TT genotype was associated with PCa, both with and without adjustment for age (P < 0.010 and P = 0.047, respectively). The TT genotype was also associated with the moderate- and high-risk PCa categories (P = 0.007 and 0.027, respectively).ConclusionThe TT genotype may represent a useful biomarker for identifying high risk of PCa and as a postoperative prognosticator in Chinese PCa patients.

Clinicopathological and Prognostic Factors in 106 Prostate Cancer Patients Aged ≤55 Years: A Single-Center Study in China.

BackgroundEarly-onset prostate cancer patients (aged ≤55 years) from Western countries have been well characterized in previous studies. However, the clinicopathological and prognostic characteristics of early-onset Chinese prostate cancer patients have not yet been assessed. This study aimed to examine the clinicopathological and prognostic factors of prostate cancer patients aged ≤55 years in a single Chinese center.Material/MethodsOne hundred six prostate cancer patients aged ≤55 years with complete clinicopathological data who were treated at our hospital between January 2000 and June 2014 were selected for this study. Survival rate was investigated by Kaplan-Meier analysis, and prognostic factors were examined by univariate and multivariate analysis.ResultsThe median time from the onset of symptoms to diagnosis was 3.5 months (range, 2–55 months). The median time after endocrine therapy to development of androgen-independent prostate cancer was 10.5 months. A total of 54 patients died (50.9%), of whom 96.2% died from prostate cancer. The 1-, 3-, and 5-year overall survival rates were 88.7%, 66.2%, and 36.0%, respectively. Univariate and multivariate analysis showed that T staging, visceral metastasis, pathological pattern, and Gleason sum were independent prognostic factors in these patients.ConclusionsProstate cancer patients aged ≤55 years are often omitted or misdiagnosed in China. Furthermore, the pathology patterns in this age group were mostly complicated with a high degree of malignancy. Late staging, visceral metastasis, pathological pattern, and high Gleason score were independent prognostic factors in these patients. Comprehensive therapy combined with local therapy is an effective treatment strategy.

NKAIN2 functions as a novel tumor suppressor in prostate cancer.

Recurrent chromosome breakpoints at 6q22.31, leading to truncation and potential loss-of-function of the NKAIN2 gene, in Chinese prostate cancer patients were previously identified. In this study we investigated genomic, methylation and expression changes of NKAIN2 in a large number of prostate cancer samples and determined its functional role in prostate cancer cells. Fluorescence in situ hybridization analysis confirmed that NKAIN2 truncation is specific to Chinese while deletion of the gene is frequent in both Chinese and UK prostate cancers. Significantly reduced expression of NKAIN2 was also detected at both RNA and protein levels. Somatic mutations of NKAIN2 in prostate cancer samples exist but at very low frequency, suggesting that it is a putative tumor suppressor gene (TSG) with haploid insufficiency. Our functional studies showed that overexpression of NKAIN2 in prostate cancer cells inhibits cellular growth by promoting cell apoptosis, and decreasing cell migration and invasion. Conversely, knockdown of NKAIN2 promotes prostate cancer cell growth by inhibiting cell apoptosis, and increasing cell migration and invasion. These data imply that NKAIN2 is a novel TSG whose activity is commonly reduced in prostate cancer. It may restrain the disease development and progression by inducing apoptosis and suppressing cancer cell growth, migration and invasion. This study provides new insights into prostate carcinogenesis and opportunities for development of novel therapies for prostate cancer.

Peripheral monocyte count: an independent diagnostic and prognostic biomarker for prostate cancer - a large Chinese cohort study.

Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 × 109 l−1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen (PSA), free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival (hazard ratio = 2.244, P < 0.05) and overall survival (hazard ratio = 1.995, P < 0.05), but not progression-free survival (P = 0.117). Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.

TMPRSS2:ERG fusion gene occurs less frequently in Chinese patients with prostate cancer.

Prostate cancer is the commonest male malignancy in the Western world, but its morbidity is much lower in China. The principal aim of this study was to evaluate the frequency of TMPRSS2:ERG fusion in Chinese prostate cancer patients using immunohistochemistry and reverse transcription polymerase chain (RT-PCR). In addition, we compared the ERG protein expression with TMPRSS2:ERG fusion gene. The relationship between ERG expression and clinicopathologic features was also examined. Samples from patients who underwent radical prostatectomies in Changhai Hospital (Shanghai, China) were collected and stored in ethically approved tissue banks. One hundred seventy-four prostate cancer tissue samples and 10 normal tissues were marked on standard hematoxylin-eosin (HE) sections, punched out of the paraffin blocks and inserted into a recipient block using tissue arrayer instruments. Immunohistochemistry and RT-PCR were employed to detect TMPRSS2:ERG fusion gene. ERG was highly expressed in the nuclei of endothelial cells of vessels and weak cytoplasmic staining was occasionally observed. ERG positive staining was present in 14.9% (26/174) of the tumor samples in microarray. All benign prostate samples were found to be negative. RT-PCR results revealed that 11.1% (15/135) were TMPRSS2:ERG fusion positive. Altogether, there was a good agreement of ERG immunostaining with the presence of TMPRSS2:ERG. However, no correlation was observed between ERG expression and age, Gleason score, stage, surgical margin, and seminal vesicle involvement in Chinese patients. In the present study, we identified a high correlation between ERG expression and ERG TMPRSS2:ERG, with 100% sensitivity and 88.9% specificity. The expression level of ERG was unrelated to the age, Gleason score, stage, surgical margin, and seminal vesicle involvement. Therefore, the association between ERG expression and prostate cancer based on Chinese population should be further investigated in the future.

Identification of Pathogen Signatures in Prostate Cancer Using RNA-seq.

Infections of the prostate by bacteria, human papillomaviruses, polyomaviruses, xenotropic murine leukemia virus (MLV)-related gammaretroviruses, human cytomegaloviruses and other members of the herpesvirus family have been widely researched. However, many studies have yielded conflicting and controversial results. In this study, we systematically investigated the transcriptomes of human prostate samples for the unique genomic signatures of these pathogens using RNA-seq data from both western and Chinese patients. Human and nonhuman RNA-seq reads were mapped onto human and pathogen reference genomes respectively using alignment tools Bowtie and BLAT. Pathogen infections and integrations were analyzed in adherence with the standards from published studies. Among the nine pathogens (Propionibacterium acnes, HPV, HCMV, XMRV, BKV, JCV, SV40, EBV, and HBV) we analyzed, Propionibacterium acnes genes were detected in all prostate tumor samples and all adjacent samples, but not in prostate samples from healthy individuals. SV40, HCMV, EBV and low-risk HPVs transcripts were detected in one tumor sample and two adjacent samples from Chinese prostate cancer patients, but not in any samples of western prostate cancer patients; XMRV, BKV and JCV sequences were not identified in our work; HBV, as a negative control, was absent from any samples. Moreover, no pathogen integration was identified in our study. While further validation is required, our analysis provides evidence of Propionibacterium acnes infections in human prostate tumors. Noted differences in viral infections across ethnicity remain to be confirmed with other large prostate cancer data sets. The effects of bacterial and viral infections and their contributions to prostate cancer pathogenesis will require continuous research on associated pathogens.

Androgen deprivation therapy, diabetes and poor physical performance status increase fracture risk in Chinese men treated for prostate cancer

We investigated the fracture risk after androgen deprivation therapy (ADT) for prostate cancer in the Chinese population. All Chinese prostate cancer patients who were treated primarily by radical prostatectomy or radiotherapy, with or without further ADT, from year 2000 to 2009 were reviewed. We compared the fracture risk in patients who were given ADT (ADT group) with those who were not given any ADT (non-ADT group). Potential risk factors including age, diabetes mellitus, hypertension, hyperlipidemia, ischemic heart disease and performance status were reviewed. The fracture risk was analyzed with Kaplan–Meier and multivariate Cox regression analyses. Our cohort consisted of 200 patients in the non-ADT group and 252 patients in the ADT group. The ADT group was shown to have higher fracture risk (p = 0.036) upon Kaplan–Meier analysis. Upon multivariate Cox regression analyses, diabetes mellitus (HR 4.39, 95% CI 1.08–17.83, p = 0.039), poor performance status (HR 3.14, 95% CI 1.24–8.00, p = 0.016) and the use of ADT (HR 4.89, 95% CI 1.03–23.17, p = 0.045) were associated with increased fracture risk. In conclusion, the fracture risk should be considered while deciding on ADT in Chinese men, especially in diabetic patients with poor performance status.

Outcomes of patients with lymph node metastasis treated with radical prostatectomy and adjuvant androgen deprivation therapy in a Chinese population: results from a cohort study.

BackgroundThe aim of this study is to assess the prognosis of prostate cancer (PCa) with lymph node metastases (LNM) detected in pelvic lymph node dissection (PLND) after radical prostatectomy (RP) and adjuvant androgen deprivation therapy (ADT) in a Chinese population.MethodsFrom June 2005 to September 2012, the medical histories of 67 Chinese PCa patients with LNM detected after RP and extended PLND were collected, and all these patients received continuous adjuvant ADT. Postoperative survival was estimated using the Kaplan-Meier method. The impact of various clinicopathological factors on outcome was analyzed using Cox proportional hazard regression models. All tests were two-sided with P < 0.05 considered significant.ResultsMedian follow-up was 46.7 months, and two patients were lost to follow-up. Five-year event-free survival for patients with positive lymph nodes was 93.0%, 83.0%, and 96.0% for local recurrence, systemic progression, and cancer death, respectively. One-year, 2-year, and 3-year biochemical recurrence (BCR)-free survival was 52%, 40%, and 22%, respectively. Postoperative BCR-free survival was 25.7 months. BCR-free survival for patients with a single LNM was longer than those with two or more LNM (median 39.1 months vs. median 17.2 months, P = 0.002). In a multivariate Cox model, only two or more LNM was a significant predictor of BCR (hazard ratio 2.6, P = 0.005).ConclusionsDespite low BCR-free survival, Chinese patients with LNM can benefit from RP and adjuvant ADT. Patients with low nodal metastatic burden had a favorable prognosis.

Adiponectin as a potential tumor suppressor inhibiting epithelial-to-mesenchymal transition but frequently silenced in prostate cancer by promoter methylation.

Recent evidence suggests a particular role for obesity in prostate cancer (PCa) progression. Adiponectin (ADN) is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of PCa cell proliferation. Although serum ADN levels have been identified to be related with carcinogenesis in a tissue-specific context, the exact role of endogenous ADN in PCa cells remains largely unknown. Two tissue microarrays were constructed and immunohistochemistry (IHC) was utilized to detect ADN's expression in a cohort of 96 Chinese PCa patients with radical prostatectomy as well as 15 cases with Benign Prostatic Hyperplasia (BPH). MTS and transwell assays were applied to validate the effects of ADN on proliferation and invasive capacity of PCa cells. Real-time PCR and Western blot were performed to evaluate the expression at transcript and protein levels. Epigenetic modifications of ADN's promoter after TGF-β1 treatment in 22RV1 cells was monitored by chromatin immunoprecipitation (ChIP). Methylation-Specific PCR (MSP) was performed to determine the methylation status of ADN's promoter. IHC showed decreased levels of ADN in 1 of 15 (6.7%) BPH cases, 6 of 27 (22.2%) PCa cases with low Gleason score (<7), 18 of 26 (69.2%) cases with Gleason score 7, but 32 of 43 (74.4%) cases with high Gleason score (>7). Silencing endogenous ADN could promote proliferation and invasion of 22RV1 cells via orchestrating Epithelial-to-mesenchymal Transition (EMT) process. TGF-β1, a potent EMT inducer, could decrease levels of chromatin markers associated with active genes (H3K4me3, H4acetylK16), and increase levels of repressive marker (H3K27me3) at ADN promoter in 22RV1 cells. Additionally, 5-aza and TSA treatment restored ADN expression in LNCaP cells in which the ADN expression was almost absent. MSP analysis revealed that methylation in the promoter might be involved in decreased expression of ADN in PCa tissues. Our findings indicated that endogenous ADN may function as a tumor suppressor gene through inhibiting EMT of PCa cells but is down-regulated in PCa via promoter hypermethylation.

Cognitive function in Chinese prostate cancer patients on androgen-deprivation therapy: A cross-sectional study.

Androgen-deprivation therapy (ADT) is a main treatment option for patients with prostate cancer (PCa), but its effect on cognition remains unclear. The primary purpose of this cross-sectional case-control study was to evaluate the effects of ADT on cognition in Chinese PCa patients. Participants included PCa patients who had undergone ADT (ADT group, n = 33) and patients who did not undergo ADT (non-ADT group, n = 32), as well as age- and education-matched healthy controls (HC group, n = 35). All participants were examined using the neuropsychological battery aimed at assessing several cognitive domains including attention, memory and information processing performance. The ADT group obtained significantly worse scores than the non-ADT and HC groups in the following neuropsychological tests: Recognition (P < 0.01), WAIS Digit Span forward (P < 0.05), Trailmaking B (P < 0.01) and Stroop Interference test (P < 0.01). No significant difference was found between the non-ADT and HC groups (P > 0.05). Chinese PCa patients receiving ADT showed cognitive impairments in several domains including memory, attention and information processing performance.

Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients from northern India.

BACKGROUNDMolecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene‐rearrangements, PTEN deletion, and SPINK1 over‐expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over‐expression, and PTEN deletion in this cohort.METHODSIn this multi‐center study, formalin‐fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA‐ISH) and/or fluorescence in situ hybridization (FISH).RESULTS ERG over‐expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA‐ISH, no alteration in ETV4 was observed. SPINK1 over‐expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG‐positive cases (P = 0.017) but in only one case with SPINK1 over‐expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in ∼1% and ∼4.5% of the PCa cases, respectively.CONCLUSIONSThis is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over‐expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in clinical decision‐making for the pursuit of surgery, diagnosis, and in selection of therapeutic intervention. Prostate 75:1051–1062, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population living in Hong Kong.

Previous reports on the risk of stroke after androgen deprivation therapy for prostate cancer were largely based on Caucasians. We investigated the risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. All Chinese prostate cancer patients who were treated primarily with radical prostatectomy or radiotherapy, with (androgen deprivation therapy group) or without (non-androgen deprivation therapy group) further androgen deprivation therapy, at our hospital from year 2000-09 were reviewed. Potential risk factors of ischemic stroke including age, baseline prostate-specific antigen, Gleason score, clinical T stage, hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, history of stroke, use of androgen deprivation therapy and duration of androgen deprivation therapy were reviewed. The risk of ischemic stroke after androgen deprivation therapy was analyzed with Kaplan-Meier and multivariate Cox regression analyses. A total of 452 patients were included, consisting of 200 patients in the non-androgen deprivation therapy group and 252 patients in the androgen deprivation therapy group. The androgen deprivation therapy group appeared to have increased risk of ischemic stroke when compared with the non-androgen deprivation therapy group (P = 0.063) upon Kaplan-Meier analysis. Upon multivariate Cox regression analyses, older age (hazard ratio 1.13, 95% confidence interval 1.04-1.22, P = 0.003), hyperlipidemia (hazard ratio 4.61, 95% confidence interval 2.01-10.54, P < 0.001) and the use of androgen deprivation therapy (hazard ratio 3.32, 95% confidence interval 1.14-9.67, P = 0.028) were associated with increased risk of ischemic stroke. There was increased risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. The risk of ischemic stroke should be considered while deciding on androgen deprivation therapy, especially in older patients with known history of hyperlipidemia.

Incidental prostate cancer in Asian men: high prevalence of incidental prostatic adenocarcinoma in Chinese patients undergoing radical cystoprostatectomy for treatment of bladder cancer and selection of candidates for prostate-sparing cystectomy.

Previous studies report a low prevalence of incidental prostate cancer in Chinese patients (3-7%). We evaluated incidental prostatic adenocarcinoma (PCa) and urothelial carcinoma (UCa) involvement of the prostate in cystoprostatectomy specimens. We analyzed 340 cystoprostatectomy specimens from patients who underwent radical cystoprostatectomy for the treatment of bladder cancer in China from 2004 to 2014. None of the patients had known prostate cancer prior to cystoprostatectomy. Overall, 180 (53%) patients had either PCa or UCa in the prostate. We found that 95 (28%) had PCa and 115 (34%) had UCa involvement of prostate. The rate of incidental prostate cancer was 21% and 31%, respectively, from two study periods (2004-2008 and 2009-2014). Among the 95 patients with PCa, 19 (20%) had Gleason score of ≥7, nine (10%) had PCa tumor volume >0.5 cc, and eight (8.4%) had extracapsular extension. Of the 115 with prostatic UCa, 61 had prostatic urethra and/or periurethral prostatic duct involvement only, while 54 had prostatic stromal invasion. Age (odds ratio [OR] = 1.04, P = 0.001), increasing stage of bladder tumor (OR = 1.28, P = 0.005), multifocal tumors of bladder (OR = 3.22, P < 0.001), carcinoma in situ (CIS) in the bladder (OR = 5.52, P < 0.001), and bladder neck involvement (OR = 6.12, P < 0.001) were strongly associated with prostatic UCa. The rate of incidental PCa in cystoprostatectomy specimens in China has increased over the last decade. Patients with advanced age, elevated serum PSA level, advanced bladder tumor stage, multifocal bladder tumors, CIS in the bladder, and tumor location at the bladder neck should be excluded as candidates for prostate-sparing cystectomy.

The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy.

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096–2.545, P= 0.017), and a 1.5-fold increased risk of pT3–4 disease (OR = 1.583, 95% CI 1.106–2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038–2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.

Prevalence and Risk Factors of Prostate Cancer in Chinese Men with PSA 4-10 ng/mL Who Underwent TRUS-Guided Prostate Biopsy: The Utilization of PAMD Score.

Purpose. To elucidate the characteristics and risk factors for positive biopsy outcomes in Chinese patients with prostate specific antigen (PSA) 4–10 ng/mL and develop a risk-stratification score model. Methods. The data of 345 patients who underwent transrectal ultrasound-guided prostate biopsy between 2011 and 2013 was retrospectively analyzed. Digital rectal examination (DRE), prostate volume (PV), magnetic resonance imaging (MRI), and smoking status were also collected. Positive biopsy outcomes were defined as prostate cancer (PCa) and high grade PCa (HGPCa, Gleason Score ≥ 7). Results. The median PSA was 7.15 (IQR 5.91–8.45) ng/mL. Overall 138 patients (40.0%) were shown to have PCa, including 100 patients (29.0%) with HGPCa. Smaller PV, elder age, MRI results, and positive DRE were proved to be predictive factors for positive biopsy outcomes in both univariate and multivariate analysis. We developed a “PAMD” score which combined the four factors to categorize patients into three risk groups, and the model performed good predictive sensitivity and specificity. Conclusion. The prevalence of prostate cancer in Chinese patients with PSA 4–10 ng/mL was 40%, including 29% patients with high grade disease. DRE, age, MRI, and PV were predictive factors for positive biopsy outcomes, and the PAMD score model could be utilized for risk-stratification and decision-making.

Overexpression of ETV4 is associated with poor prognosis in prostate cancer: involvement of uPA/uPAR and MMPs.

ETS gene fusions involving ERG, ETV1, ETV4, ETV5, and FLI1 define a distinct class of prostate cancer (PCa), and this might have a bearing on diagnosis, prognosis, and rational therapeutic targeting. In the current study, we focused on the clinicopathological significance of ETV4 in Chinese PCa patients and the mechanisms whereby ETV4 overexpression mediates tumor invasion in the prostate. Overall, ETV4 overexpression was identified in 30.4 % (45/148) of PCa cases by immunohistochemistry. Accordingly, ETV4 was rearranged in only 1.6 % (2/128) of PCa patients. Clinically, ETV4 overexpression was significantly correlated with Gleason score (P = 0.045) and pathological tumor stage (P = 0.041). Multivariate Cox regression analysis indicated that ETV4 is an unfavorable independent prognostic factor (P = 0.040). Functional studies further showed that small interfering RNA (siRNA) knockdown of ETV4 significantly decreases proliferation and invasion of PC-3 cell and partially reverses epithelial-mesenchymal transition in vitro. Notably, ETV4 knockdown significantly downregulated expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) at messenger RNA (mRNA) and protein levels. Chromatin immunoprecipitation assay demonstrated that ETV4 regulates uPA expression through direct binding to its promoter region. Additionally, ETV4 knockdown was also observed to significantly inhibit expression of matrix metalloproteinase (MMP)-2 and MMP-9. In conclusion, for the first time, our study suggested that ETV4 is an independent poor prognostic factor in Chinese PCa patients. Silencing of ETV4 suppresses invasion of PCa cells by inhibiting the expression of uPA/uPAR as well as MMPs. Further studies will be needed to determine whether ETV4 could be regarded as a potential target for the management and prevention of PCa.