Trichomonas vaginalis infection and prostate-specific antigen concentration: Insights into prostate involvement and prostate disease risk

Background: The protist Trichomonas vaginalis causes a common, sexually transmitted infection and has been proposed to contribute to the development of chronic prostate conditions, including benign prostatic hyperplasia and prostate cancer. However, few studies have investigated the extent to which it involves the prostate in the current antimicrobial era. We addressed this question by investigating the relation between T. vaginalis antibody serostatus and serum prostate-specific antigen (PSA) concentration, a marker of prostate infection, inflammation, and/or cell damage, in young, male, US military members. Methods: We measured T. vaginalis serum IgG antibodies and serum total PSA concentration in a random sample of 732 young, male US active duty military members. Associations between T. vaginalis serostatus and PSA were investigated by linear regression. Results: Of the 732 participants, 341 (46.6%) had a low T. vaginalis seropositive score and 198 (27.0%) had a high score, with the remainder seronegative. No significant differences were observed in the distribution of PSA by T. vaginalis serostatus. However, slightly greater, nonsignificant differences were observed when men with high T. vaginalis seropositive scores were compared with seronegative men, and when higher PSA concentrations were examined (≥0.70 ng/mL). Specifically, 42.5% of men with high seropositive scores had a PSA concentration greater than or equal to 0.70 ng/mL compared with 33.2% of seronegative men (adjusted P = .125). Conclusions: Overall, our findings do not provide strong support for prostate involvement during T. vaginalis infection, although our suggestive positive findings for higher PSA concentrations do not rule out this possibility entirely. These suggestive findings may be relevant for prostate condition development because higher early- to mid-life PSA concentrations have been found to predict greater prostate cancer risk later in life.     

Perioperative complications of radical retropubic prostatectomy in patients with locally advanced prostate cancer: a comparison with clinically localized prostate cancer

Radical prostatectomy (RP) continues to be an effective surgical therapy for prostate carcinoma, particularly for organ-confined prostate cancer (PCa). Recently, RP has also been used in the treatment of locally advanced prostate cancer. However, little research has been performed to elucidate the perioperative complications associated with RP in patients with clinically localized or locally advanced PCa. We sought to analyse the incidence of complications in these two groups after radical retropubic prostatectomy (RRP). From June 2002 to July 2010, we reviewed 379 PCa patients who underwent RRP in our hospital. Among these cases, 196 had clinically localized PCa (T_1a–T_2c: group 1), and 183 had locally advanced PCa (≥T_3a: group 2). The overall complication incidence was 21.9%, which was lower than other studies have reported. Perioperative complications in patients with locally advanced PCa mirror those in patients with clinically localized PCa (26.2% vs. 17.8%, P=0.91). Our results showed that perioperative complications could not be regarded as a factor to consider in regarding RP in patients with cT₃ or greater.     

Comprehensive analysis of alternative splicing profiling reveals novel events associated with prognosis and the infiltration of immune cells in prostate cancer

BackgroundAlternative splicing (AS) is believed to play a vital role in tumor development. Therefore, comprehensive investigation of AS and its biological function in prostate cancer (PCa) is crucial.MethodsThe AS profiling of 489 patients with PCa was obtained from The Cancer Genome Atlas (TCGA) SpliceSeq database. Bioinformatics tools were used to describe splicing associations and build prognostic models. Unsupervised clustering of the determined prognostic AS events and the relationship with immune characteristics were also explored.ResultsIn total, 20,723 AS events were detected and 2,805 were identified in PCa. In the regulatory networks, the data suggested a significant correlation between splicing factor (SF) expression and AS events. To stratify the progression risk of PCa patients, prognostic models were constructed using splicing patterns. Six AS events were screened out as independent prognostic factors for progression-free survival. Based on the gene features, we constructed the combined prognostic predictors model, and the receiver operating characteristic (ROC) curve for this model reached a high area under the ROC curve (AUC) of 0.729793, indicating a favorable ability to predict patient outcomes. Through unsupervised clustering analysis, the correlations between AS-based clusters and prognosis as well as immune characteristics were revealed. The correlation analysis on TIMER revealed the relationship between gene expression and immune cell infiltration.ConclusionsThis in-depth genome-wide analysis of the AS profiling in PCa revealed unique AS events associated with cancer progression and the infiltration of immune cells, with potential for predicting outcomes and therapeutic responses.     

Investigations of prostate epithelial stem cells and prostate cancer stem cells

Although both prostate epithelial stem cells and prostate cancer stem cells are implicated in the differentiation of the normal prostate gland and carcinogenesis of prostate cancer, there has, until recently, been little information regarding their biology. This review summarizes the recent advancements in cell biological research including various in vitro culture systems that have offered the characterization and isolation of prostate epithelial stem cells and prostate cancer stem cells. In addition, the stromal niche or microenvironment of stem cells plays an essential role in proliferation and differentiation of normal stem cells. Stroma surrounding cancer cells, which also provide another unique niche, may involve the initiation and development of cancer stem cells. Investigation of stem cells and their microenvironments in the prostate should lead to the elucidation of biological features and the development of novel treatments for prostate cancer.     

前列腺癌肿瘤组织中E-cadherin和N-cadherin的表达及意义

目的:探讨上皮-间质转化(EMT)相关蛋白E-cadherin和N-cadherin在中低危前列腺癌和高危前列腺癌中的表达差异,以及E-cadherin和N-cadherin的表达与患者年龄、血清PSA水平、肿瘤组织Gleason评分的关系。方法:回顾性分析42例前列腺癌患者临床资料,将前列腺癌分为高危组27例和中低危组15例。免疫组化法检测两组E-cadherin和N-cadherin的表达,并比较两组有无差异;同时分析E-cadherin和N-cadherin的表达阳性率与血清PSA值、肿瘤Gleason评分及患者年龄的关系。结果:E-cadherin在中低危组的表达水平高于高危组(6.1±0.51 vs 4.2±0.37,P0.01),并且在中低危组中表达阳性率显著高于高危组(73.3%vs 25.9%,P0.01),E-cadherin在PSA20μg/L的患者中表达阳性率高于PSA≥20μg/L的患者(66.7%vs 29.6%,P0.05),在Gleason评分5~7分的患者中,其表达阳性率明显高于Gleason评分8~10分的患者(60.9%vs 21.1%,P0.05)。N-cadherin在中低危组的表达水平低于高危组(3.7±0.32 vs 7.5±0.58,P0.01),并且在中低危组中的表达阳性率低于高危组中(13.3%vs 59.3%,P0.05),在Gleason评分5~7分的患者中,其表达阳性率明显低于Gleason评分8~10分的患者(26.1%vs 63.2%,P0.05),N-cadherin在PSA20μg/L和PSA≥20μg/L的患者中表达阳性率没有差异(P0.05)。E-cadherin和N-cadherin在年龄≥70岁和70岁的患者中表达阳性率均没有明显差异(P0.05)。结论:E-cadherin和N-cadherin在高危前列腺癌和中低危前列腺癌表达阳性率及表达水平存在差异,即两者与前列腺癌的侵袭转移有关,并且E-cadherin和N-cadherin的表达可能与前列腺癌Glesaon评分、血清PSA水平有关。     

不同前列腺癌细胞系及其皮下肿瘤上皮间质转化特性鉴定

目的:通过比较不同人前列腺癌细胞系在SC ID鼠皮下成瘤特性,鉴定前列腺癌细胞系及其皮下肿瘤上皮、间质标志蛋白的表达情况,探讨前列腺癌细胞系成瘤过程与上皮-间质转化(EMT)之间关系。方法:将DU145、Tsu、PC3和LNCaP 4种人前列腺癌细胞系分别接种于SC ID鼠皮下,比较其成瘤特性;用W estern印迹法鉴定人前列腺癌细胞系及其相应皮下肿瘤钙粘蛋白、波形纤维蛋白的表达,并比较其成瘤前后的区别,探讨上皮间质转化与成瘤的关系。结果:EMT阳性细胞(DU145和Tsu)成瘤率、成瘤速度高于EMT阴性细胞(PC3和LNCaP),4种细胞系成瘤的上皮性的标志蛋白钙粘蛋白表达出现不同变化:DU145表达下调,PC3、LNCaP表达缺失,Tsu表达上调,共同特点是间质性的标志蛋白波形纤维蛋白表达消失。结论:EMT阳性细胞成瘤能力高于EMT阴性细胞,皮下肿瘤的形成过程中的确存在间质-上皮转化(MET)现象。     

The association of prostate stem cell antigen (PSCA) mRNA expression and subsequent prostate cancer risk in men with benign prostatic hyperplasia following transurethral resection of the prostate

BACKGROUND: Prior data showed prostate stem cell antigen (PSCA) mRNA expression in benign prostatic hyperplasia (BPH) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression in resected BPH samples was associated with the subsequent presence of cancer following transurethral resection of the prostate (TURP). METHODS: PSCA in situ hybridization was performed on the TURP-resected tissues from 288 patients, who were histopathologically confirmed BPH without cancer. All these patients were continuously followed for 9-70 months postoperatively. Univariate and multivariate cox regression analyses were used to evaluate the predictive performance of PSCA mRNA for subsequent cancer onset following TURP. RESULTS: PSCA mRNA was detected in 93/288 (32.3%) of the resected BPH specimens, with a mean positive-labeling cells of 23.8%, in which 22 patients (23.7%) were identified as having PCa on follow-up. Of 195 patients with negative expression for PSCA mRNA 2 (1.0%) were subsequently found with PCa. PSCA mRNA expression levels were directly proportional to higher Gleason score and clinical T stage. Univariate and multivariate cox regression analyses demonstrated that only PSCA mRNA expression was predictive of the subsequent cancer development after TURP, however, PSA velocity was an univariately significant but not multivariately significant predictor. CONCLUSIONS: This prospective study identifies PSCA mRNA in BPH as a significant predictor of cancer development after TURP, suggesting that PSCA may be used to identify patients who are at high risk for subsequent cancer onset following TURP for BPH and the PSCA test may be useful when applied for repeat biopsies.     

Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer

BackgroundAs a new-generation androgen-receptor antagonist, enzalutamide is a first-choice drug for advanced prostate cancer (PCa) patients. However, secondary resistance to enzalutamide poses a new challenge in the treatment of cancer. Long non-coding RNA (lncRNA) regulates cell function through many levels and mechanisms, and also plays an important role in the biological behaviors of tumors.MethodsLncRNA microarrays were used to detect enzalutamide-resistant related lncRNA in Enzalutamide-resistant C4-2 (C4-2 ENZ-R) cells and corresponding parent cells. Cell Counting Kit 8, flow cytometry, and transwell assays were used to test the effect of lncRNA NONHSAT210528 on the function of PCa cells. RNA pulls down and the luciferase report gene was used to detect the competitive endogenous RNA (ceRNA) mechanism. The culture supernatant of C4-2 and C4-2b cells was transferred to the lower chamber for transwell assay of human umbilical endothelial cells (HUVECs).ResultsThe lncRNA microarray analysis showed that there were significant differences in the expression of many lncRNAs between the C4-2 ENZ-R and C4-2 cells. The real-time polymerase chain reaction (PCR) detection showed that the expression of lncRNA NONHSAT210528 was significantly higher in the C4-2 ENZ-R cells than the C4-2 cells. The Transwell assays showed that lncRNA NONHSAT210528 overexpression increased the invasion of the C4-2 and C4-2b cells. The cell-wound scratch and the transwell assays showed that the culture supernatant of C4-2 and C4-2b cells with overexpressed lncRNA NONHSAT210528 promoted the migration and invasion of HUVECs. Furthermore, lncRNA NONHSAT210528 regulated the expression of YOD1 dependent on miR-21.ConclusionsEnzalutamide-resistant related lncRNA NONHSAT210528 appears to promote the proliferation and invasion of PCa cells by functioning as a ceRNA and regulating the miR-21-5p/YOD1 signal pathway.