血清PSA含量与前列腺癌临床分期、病理分级的相关性

目的:探讨血清前列腺特异性抗原(PSA)与前列腺癌(PCa)临床分期、病理分级的相关性.方法:对自2004年7月～2009年12月南京市13692例50岁以上的男性在健康体检时行血清PSA检测.以PSA≥4.0ng/ml定为前列腺癌可疑病例.建议行前列腺穿刺活检以确诊.共筛查出PCa患者140例,比较不同PSA值PCa患者的Gleason评分及临床分期.结果:随着PSA值的升高,前列腺癌筛查阳性率亦随之升高,低分化前列腺癌患者血清PSA含量明显高于高分化前列腺癌和中分化前列腺癌患者(P＜0.05),晚期前列腺癌患者血清PSA含量明显高于早期PCa患者(P＜0.01).血清PSA含量≥20ng/ml的前列腺癌人群中低分化前列腺癌及晚期前列腺癌的比例高于血清PSA含量＜20ng/ml的前列腺癌人群(P＜0.01).结论:血清PSA可以为前列腺癌患者的诊断、治疗及预后判断提供重要依据.     

前列腺特异性抗原在前列腺癌诊断中的应用进展

已经证明,前列腺特异性抗原（PSA）是一种有价值的前列腺癌（PCa)肿瘤标记物,血清PSA的广泛使用提高了前列腺癌的检出率,使晚期癌患得明显减少。然而,PSA对PCa的检测缺乏特异性,由于其高的假阳性率,引起许多不必要的活检。为了提高PSA对PCa诊断的特异性,降低不必要的活检,众多学正在探讨与PSA相关的几项参数的临床应用价值,本就此作一综述。     

uPCA3mRNA、tPSA、fPSA/tPSA、PSAD对PSA灰区前列腺癌诊断的临床意义

目的：探讨uPCA3mRNA、tPSA、fPSA/tPSA、PSAD对PSA 灰区前列腺癌的诊断价值。方法：经前列腺穿刺活检诊断为前列 腺增生(BPH) 111 例和前列腺癌(PCa) 89 例,测定血清tPSA、fPSA 与前列腺体积,所有病例均计算fPSA／tPSA、PSAD。用 RT-PCR 的方法检测PSA mRNA、PCA3 mRNA 的含量,以PCA3 mRNA/PSA mRNA 表示PCA3 mRNA 的含量。比较两组间 tPSA、fPSA/tPSA、PSAD 及PCA3mRNA各指标的差异,分析各指标在ROC 曲线下的面积、各指标的诊断敏感性和特异性。结果： PCa 组的fPSA／tPSA较BPH 组降低（P<0.01）,PCa 组的tPSA、PSAD及PCA3 mRNA较BPH 组均升高（P<0.01）。tPSA、fPSA／ tPSA、PSAD及PCA3 mRNA在ROC 曲线下的面积从大到小依次是PCA3 mRNA>PSAD > fPSA ／tPSA>tPSA。当PCA3 mRNA 和PSAD 临界值分别为0.27 和0.15 时,诊断PCa 的敏感性和特异性分别是86.5%和77.5%,80.9%和55.9%。结论：uPCA3 mRNA、fPSA／tPSA、PSAD 的测定能显著提高灰区PCa 诊断的敏感性和特异性,且uPCA3 mRNA 诊断效能最高。     

PSA相关指标对前列腺癌诊断价值的评价及比较研究

目的:探讨血清总PSA(TPSA)、F/TPSA和PSA密度(PSAD)在前列腺癌(PCa)诊断中的价值,寻找更准确的前列腺癌诊断指标。方法:采用化学发光免疫分析法检测前列腺癌患者(60例)和前列腺增生患者(240例)的血清PSA水平,通过B超测定患者前列腺的体积,计算PSAD,运用ROC曲线评价和比较血清总PSA(TPSA)、F/TPSA和PSAD诊断前列腺癌的准确性和特异性。结果:(1)前列腺癌患者TPSA和PSAD值均明显高于前列腺增生患者(P0.01),F/TPSA明显低于前列腺增生患者(P0.01);(2)TPSA阈值定为4 ng/ml时,诊断前列腺癌的敏感性、特异性分别为56.23%、80.10%。F/TPSA阈值定为0.15时,诊断前列腺癌的敏感性、特异性分别为88.10%、69.10%,PSAD阈值定为0.20时,诊断前列腺癌的敏感性、特异性分别为88.60%、88.30%。结论:TPSA、F/TPSA和PSAD在前列腺癌诊断中均有一定的价值,且PSAD诊断前列腺癌的敏感性、特异性优于TPSA、F/TPSA,是诊断前列腺癌更为理想的指标。     

m6A甲基化修饰在前列腺癌发生发展中的调控机制

N6-腺苷甲基化(N6-adenosine methylation)是腺苷N6位点的甲基化形式，常出现在真核生物的mRNA中，是最常见的RNA内部修饰的方式之一。研究表明，m6A通过调节基因的表达来影响细胞的生物过程；同时m6A的调控因子也在各种癌症的发生、发展中发挥着关键作用。前列腺癌(prostate cancer, PCa)是一种常见的男性恶性肿瘤，超过60岁的男性的患病风险逐年攀升，并且随着人口老龄化的问题，可以预计PCa的患病数目会继续升高。近年来，关于m6A在肿瘤发生发展中的作用逐渐受到广泛关注，但是m6A甲基化修饰在PCa中的研究仍然有限，因此，进一步探讨二者之间的关系显得尤为重要。本文综述了近年来关于m6A甲基化修饰在PCa中的作用、机制及应用的研究进展，尤其详细综述了METTL3,FTO,YTHDF2三种经典的m6A相关调控蛋白质在PCa中的作用机制；并阐述了m6A在晚期PCa(例如：去势抵抗性前列腺癌，骨转移性前列腺癌)中的潜在应用。从甲基化修饰角度为PCa的早期诊断、治疗和预后挖掘一套有效治疗策略，为实现个体化治疗提供更多理论参考。     

联合检测血清F-PSA、T-PSA、F/T对前列腺癌的诊断意义

目的:探讨F-PSA、T-PSA及F-PSA/T-PSA(F/T)比值在前列腺癌诊断中的价值.方法:采用全自动免疫荧光分析仪检测50例正常健康体检者,78例前列腺癌患者(PCa)以及184例良性前列腺增生患者(BPH)血清中F-PSA、T-PSA及F/T比值,并对各组数值结果进行比较分析.结果:结果显示PCa组血清F-PSA、T-PSA高于BPH组及正常对照组(P＜0.01,P＜0.01);而F/T值低于BPH组及正常对照组(P＜0.01,P＜0.01).T-PSA处于4-10ng/ml时,PCa组T-PSA水平与BPH组比较无显著性差异(P＞0.05),但PCa组F/T值显著低于BPH组,两者间差异具有统计学意义(P＜0.01).结论:联合检测F-PSA、T-PSA及F/T比值对PCa的鉴别诊断及高危人群的筛查均具有重要意义.     

前列腺癌生物标记与早期诊断

前列腺癌发病率高,肿瘤晚期难以治愈,这就致使早期诊断变得尤为重要。生物标记应用于诊断和治疗已经有50年的历史了,当今前列腺特异性抗原(PSA)作为唯一应用于临床的标记,一套依赖于PSA的诊断系统已经建立。然而标记本身的缺陷限制了系统的应用。基因组学和蛋白质组学技术的发展大大加速了前列腺癌相关生物分子的研究,为发现前列腺癌的生物标记提供了广阔的前景。以前列腺癌发生的遗传背景为基础,对目前的检测标记以及检测标记的标准作了介绍。     

经直肠实时组织超声弹性成像诊断前列腺良恶性病灶的价值

目的:探索经直肠实时组织超声弹性成像技术在前列腺良恶性病灶诊断中的应用价值。方法:选取2013年12月至2014年5月我科疑似前列腺癌(PCa)并拟行穿刺活检的患者49例,以病例活检结果作为金标准,对比经直肠实时组织超声弹性成像技术、经直肠超声(TRUS)及直肠指诊(DRE)在疑似PCa患者中的诊出结果,并对直肠超声进行弹性图像评分及应变指数分析。结果:弹性图像评分≥4分时,其对PCa的敏感性、特异性及准确性分别为92.3%、91.3%和93.9%;良性病灶的应变指数为2.84±4.72,恶性病灶的应变指数为32.12±15.05,差异有统计学意义(P0.05)。结论:经直肠实时组织超声弹性成像技术可提高PCa的诊出率,在前列腺良恶性病灶的鉴别及指导治疗与预后方面有重要价值。     

GSTP1基因甲基化检测在前列腺癌临床诊断中的Meta分析

谷胱甘肽S-转移酶-pi 1(glutathione S-transferase pi 1,GSTP1)基因是多种癌症的抑制基因。目前已有多项研究探讨GSTP1基因启动子区甲基化检测在前列腺癌(prostate cancer,PCa)临床诊断中的意义,但尚无系统性评估。本研究通过检索Pub Med、Web of Science数据库,收集相关英文文献进行Meta分析,对GSTP1基因启动子区甲基化检测在PCa临床诊断中的意义做出系统性评估。最终有27篇文献,共计3 183例样本纳入本研究,包含2 067例PCa样本及1 116例对照样本。Meta分析结果,PCa患者GSTP1基因启动子区相比正常对照组呈现显著高甲基化,差异有统计学意义(OR=17.98,95%CI:12.16~26.58,p0.000 1)。不同亚组(人种,样本类型及检测方法等)组间无显著性差异。上述研究的合并敏感度及特异度分别为0.70和0.96。此外,我们从TCGA(the cancer genome atlas,TCGA)数据库中选取425例前列腺腺癌(prostate adenocarcinoma,PRAD)组织与54例癌旁组织的高通量全基因组甲基化芯片数据进行验证分析后显示,GSTP1基因启动子区9个CpG位点中的7个位点,癌症组织相比癌旁组织呈现显著高甲基化水平。其敏感度均在0.85以上,特异度及AUC区间均在0.90以上,FDR1×10~(-20)。综上,Meta分析和TCGA均显示PCa患者GSTP1基因启动子区相比正常对照组呈现显著高甲基化,且诊断特异度与敏感度均较高,是非常有前景的PCa诊断标志物,对PCa的临床诊断具有借鉴意义。     

PSA在前列腺增生和前列腺癌中的诊断价值

目的：探讨临床上检测前列腺特异性抗原（PSA）的变化情况对前列腺增生和前列腺癌等疾病的诊断价值。方法：采用回顾性分析的方法,选取2010年6月至2012年4月在我院泌尿科接受治疗的前列腺增生患者64例定义为前列腺增生组（BPH）,前列腺癌患者83例定义为前列腺癌组（PCa）,另选取同期接受体检的健康人群137例作为对照组。分别检测三组患者入院时的游离前列腺特异性抗原和总前列腺特异性抗原的水平变化情况。对比并分析三组检测结果。结果：经检测,前列腺增生患者的血清总PSA明显高于对照组健康人群的正常值,而前列腺癌患者的血清总PSA比前列腺增生患者增高的更为明显。对照组游离PSA为（2．78±0．94）ng／mL,总PSA（1．05±0．57）ng／mL,游离PSA与总PSA的比值为,（0．38±0．61）;前列腺增生患者游离PSA为（6．36＋3．24）ng／mL,总PSA为（1．64±0．76）ng／mL,游离PSA与总PSA的比值为（0．26±0．23）;前列腺癌患者游离PSA为（12．42±4．97）ng／mL,总PSA为（1．44±0．78）ng／mL,游离PSA与总PSA的比值为（0．12±0．16）。组间比较差异明显,具有统计学意义（P〈0．05）。结论：对患者的PSA进行检测,对前列腺增生和前列腺癌的诊断具有良好的辅助作用和,临床价值。     

A piece in prostate cancer puzzle: Future perspective of novel molecular signatures

Prostate cancer (PCa) has a variable biological potential. It constitutes the second most common cancer amongst men worldwide and the fifth most common cancer in Saudi Arabia. Identifying men at higher risk of developing PCa, differentiating indolent from aggressive disease and predicting the likelihood of progression will improve decision-making and selection for active surveillance protocols. Biomarkers have been utilized for PCa screening and predicting cancer behavior and response to treatment. The prostate specific antigen (PSA) screening helps detect PCa in early stages, while implementing a plan for management and outcome. However, PSA screening is still controversial, due to the risks of over diagnosis and treatment, and its inability to detect a good proportion of advanced tumors. Alternatively, a new era of PCa biomarkers has emerged with higher PCa specificity than PSA and its isoforms hopefully improving screening methods, such as Prostate Health Index (PHI) score, Progensa Prostate Cancer Antigen 3 (PCA3), Mi-Prostate Score (MiPS), Prostate Stem Cell Antigen (PSCA), 4Kscore test, and Urokinase Plasminogen Activation (uPA and uPAR). Few novel biomarkers have shown promise in preliminary results. This review will display promising biomarkers including some important FDA approved ones, highlighting their clinical implication and future place in the PCa puzzle, along with addressing their current limitations.     

Long-term survival of patients with prostate cancer in Martinique: Results of a population-based study

BackgroundMartinique has one of the highest incidences of prostate cancer (PCa) worldwide. We analysed overall survival (OS) among patients with PCa in Martinique, using data from a population-based cancer registry between 2005 and 2014.MethodsThe log-rank test was used to assess the statistical differences between survival curves according to age at diagnosis, risk of disease progression including Gleason score, stage at diagnosis and Prostate Specific Antigen (PSA). A multivariable Cox model was constructed to identify independent prognostic factors for OS.ResultsA total of 5045 patients were included with a mean age at diagnosis of 68.1±9.0 years [36.0 – 98.0 years]. Clinical stage was analysed in 4999 (99.1% of overall), 19.5% were at low risk, 34.7% intermediate and 36.9% at high risk. In our study, 8.9% of patients with available stage at diagnosis, were regional/metastatic cancers. Median PSA level at diagnosis was 10.4 ng/mL. High-risk PCa was more frequent in patients aged 65-74 and ≥75 years as compared to those aged <65 years (36.6% and 48.8% versus 28.7% respectively; p<0.0001). One-year OS was 96.3%, 5-year OS was 83.4 and 10-year OS was 65.0%. Median survival was not reached in the whole cohort. High-risk PCa (HR=2.32; p<0.0001), regional/metastatic stage (HR= 9.51; p<0.0001) and older age (65-74 and ≥75 years - respectively HR=1.70; and HR=3.38), were independent prognostic factors for OS (p<0.0001).ConclusionThis study provides long term data that may be useful in making cancer management decisions for patients with PCa in Martinique.     

Explication of the roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) as diagnostic and predictor tools for prostate cancer in equivocal PSA range of 4–10 ng/mL

BackgroundProstate cancer (PCa) is one of the most commonly encountered cancers and the leading cause of death worldwide. Currently used biomarkers accounts difficulties in discriminating benign from malignant cases or predicting outcome, so investigating new biomarkers performance is needed.ObjectivesAssessment of diagnostic and predictor roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) in PCa.Methods194 males with initial tPSA of 4–10 ng/mL were categorized into three groups: PCa, benign prostatic hyperplasia (BPH) and healthy control. Serum levels of tPSA, fPSA, p2PSA, and uPA were performed by ELISA with calculation of PHI as (p2PSA/fPSA) × √PSA.ResultsPHI and uPA were significantly higher in PCa patients relevant to BPH and healthy control (p ≤ 0.001). Both markers outperformed all assessed biomarkers and showed the highest area under the curve (AUC) in ROC curve analysis. Both were significantly higher in PCa patients with {Gleason score ≥ 7, late stages (cT2b,c; T3), LN extension and distant metastasis}relative to their counterparts. Additionally, PHI and uPA and were independent predictors of distant metastasis and Gleason score ≥ 7, while PHI was predictor of LN invasion (β = 0.25, p = 0.004).ConclusionPHI and uPA would be of potential value in discriminating between PCa, BPH and healthy men in addition, both are promising as independent predictors of adverse pathological features.     

前列腺PI-RADS V2.1评分联合血清PSA相关指标对灰区前列腺癌的诊断价值研究

摘要 目的：探讨前列腺影像报告和数据系统第2.1版（PI-RADS V2.1）评分联合血清前列腺特异抗原（PSA）相关指标对灰区前列腺癌的诊断价值。方法：回顾性分析2016年1月至2019年12月的187例经病理证实且PSA为灰区（4-10 ng/mL）的前列腺癌或前列腺增生患者资料。根据病理结果分为前列腺癌（PCa）组与前列腺增生组（BPH）组。由两名经验丰富的MRI诊断医师通过盲法对所有患者MRI图像进行PI-RADS V2.1评分,统计并计算血清PSA相关指标：总前列腺特异抗原（t-PSA）、游离前列腺特异抗原（f-PSA）、游离前列腺特异抗原与总前列腺特异抗原比值（f-PSA/t-PSA）、前列腺特异抗原密度（PSAD）。采用t检验比较各项指标在两组间的差异性,并使用受试者工作曲线（ROC）分析各项指标对灰区前列腺癌的诊断效能。结果：PI-RADS V2.1评分与PSAD在PCa与BPH组之间的差异具有统计学意义（P＜0.05）,而t-PSA、f-PSA、f-PSA/t-PSA在PCa与BPH组之间的差异均无统计学意义（P＞0.05）。根据ROC曲线分析,PI-RADS V2.1评分、PSAD、PI-RADS V2.1评分联合PSAD诊断灰区前列腺癌的曲线下面积（AUC）分别为0.814、0.671及0.838,且PI-RADS V2.1评分联合PSAD的AUC显著高于单独应用PI-RADS V2.1评分（Z=1.989,P＜0.05）与PSAD（Z=3.174,P＜0.05）。结论：PI-RADS V2.1评分与PSAD对诊断灰区前列腺癌具有较高诊断效能,且联合PI-RADS V2.1评分与PSAD能进一步提高诊断效能。     

Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer

Introduction

We previously identified prostate cancer (PCa)-associated aberrant glycosylation of PSA, where α2,3-linked sialylation is an additional terminal N-glycan on free PSA (S2,3PSA). We then developed a new assay system measuring S2,3PSA using a magnetic microbead-based immunoassay. We compared the diagnostic accuracy of conventional PSA and percent-free PSA (%fPSA) tests.

Methods

We used MagPlex beads to measure serum S2,3PSA levels using anti-human fPSA monoclonal antibody (8A6) for capture and anti-α2,3-linked sialic acid monoclonal antibody (HYB4) for detection. We determined the cutoff values in a training test and measured serum S2,3PSA levels in 314 patients who underwent biopsy, including 138 PCa and 176 non-PCa patients with PSA of <10.0 ng/ml. Serum S2,3PSA levels were presented as mean fluorescence intensity (MFI). Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of total PSA, %fPSA, and S2,3PSA.

Results

We determined an MFI cutoff value of 1130 with a sensitivity of 95.0% and specificity of 72.0% for the diagnosis of PCa in the training test. In the validation study, the area under the curve for the detection of PCa with S2,3PSA was 0.84, which was significantly higher than that with PSA or %fPSA.

Conclusions

Although the present study is small and preliminary, these results suggest that the measurement of serum S2,3PSA using a magnetic microbead-based immunoassay may improve the accuracy of early detection of PCa and reduce unnecessary prostate biopsy.     

Trends in Prostate Specific Antigen (PSA) testing and prostate cancer incidence and mortality in Australia: A critical analysis

BackgroundPopulation trends in PSA testing and prostate cancer incidence do not perfectly correspond. We aimed to better understand relationships between trends in PSA testing, prostate cancer incidence and mortality in Australia and factors that influence them.MethodsWe calculated and described standardised time trends in PSA tests, prostate biopsies, treatment of benign prostatic hypertrophy (BPH) and prostate cancer incidence and mortality in Australia in men aged 45–74, 75–84, and 85 + years.ResultsPSA testing increased from its introduction in 1989 to a peak in 2008 before declining in men aged 45–84 years. Prostate biopsies and cancer incidence fell from 1995 to 2000 in parallel with decrease in trans-urethral resections of the prostate (TURP) and, latterly, changes in pharmaceutical management of BPH. After 2000, changes in biopsies and incidence paralleled changes in PSA screening in men 45–84 years, while in men ≥85 years biopsy rates stabilised, and incidence fell. Prostate cancer mortality in men aged 45–74 years remained low throughout. Mortality in men 75–84 years gradually increased until mid 1990s, then gradually decreased. Mortality in men ≥ 85 years increased until mid 1990s, then stabilised.ConclusionAge specific prostate cancer incidence largely mirrors PSA testing rates. Most deviation from this pattern may be explained by less use of TURP in management of BPH and consequent less incidental cancer detection in TURP tissue specimens. Mortality from prostate cancer initially rose and then fell below what it was when PSA testing began. Its initial rise and fall may be explained by a possible initial tendency to over-attribute deaths of uncertain cause in older men with a diagnosis of prostate cancer to prostate cancer. Decreases in mortality rates were many fold smaller than the increases in incidence, suggesting substantial overdiagnosis of prostate cancer after introduction of PSA testing.     

A mechanistic insight into the anti-metastatic role of the prostate specific antigen

AimSince its discovery Prostate Specific Antigen (PSA), also referred to as kallikrein-3 (KLK3), has been used as standard circulating biomarker for prostate cancer (PCa). However, its specificity remains not adequate and its mechanism of action still elusive. Therefore, deciphering PSA role throughout PCa-pathobiology would be relevant in improving both cancer diagnosis and outcome prediction. We investigated the possible role played by PSA on/in the tumor microenvironment and over the first steps of cancer invasion.MethodsFresh PCa-specimens and cell lines were used for ex-vivo/in-vitro invasion assays and assessment of prostate tissue-PSA (tPSA), type 1 collagen (COL1A1) and ß1-integrin expression. Tissue Cancer Genome Atlas (TCGA) and Decipher® datasets were considered to estimate tPSA clinical relevance.ResultsA more precise, inverse, correspondence between tPSA and clinical/pathological parameters was found than for circulating PSA. KLK3 combined with Gleason grade and pathologic stage, better predicted cancer-related mortality. Consistently, we demonstrated that PSA inhibits prostate extracellular-matrix (ECM) invasion by PCa cells. As for the mechanism of action, we provided novel information that PSA is able to cleave COL1A1, a main component of the ECM. Finally, ß1-integrin, a crucial COL1A1 transducing-receptor involved in tumor adhesion/invasion, resulted to be downregulated in PCa specimens with higher levels of tPSA.ConclusionsBy interfering with type 1 collagen and its downstream targets, PSA may hamper adhesion and path of the cancer cells through ECM and their migration ability, thus explaining the inverse correlation highlighted between prostate tPSA levels and clinically significant disease.     

Changes in prostate cancer incidence,mortality and survival in relation to prostate specific antigen testing in New South Wales,Australia

BackgroundTo examine changes in prostate cancer incidence and mortality rates, and 5-year relative survival, in relation to changes in the rate of prostate specific antigen (PSA) screening tests and the use of radical prostatectomy (RP) in the Australian population.MethodsProstate cancer stage-specific incidence rates, 5-year relative survival and mortality rates were estimated using New South Wales Cancer Registry data. PSA screening test rates and RP/Incidence ratios were estimated from Medicare Benefits Schedule claims data. We used multiple imputation to impute stage for cases with “unknown” stage at diagnosis. Annual percentage changes (APC) in rates were estimated using Joinpoint regression.ResultsTrends in the age-standardized incidence rates for localized disease largely mirrored the trends in PSA screening test rates, with a substantial ‘spike’ in the rates occurring in 1994, followed by a second ‘spike’ in 2008, and then a significant decrease from 2008 to 2015 (APC −6.7, 95% CI −8.2, −5.1). Increasing trends in incidence rates were observed for regional stage from the early 2000s, while decreasing or stable trends were observed for distant stage since 1993. The overall RP/Incidence ratio increased from 1998 to 2003 (APC 9.6, 95% CI 3.8, 15.6), then remained relatively stable to 2015. The overall 5-year relative survival for prostate cancer increased from 58.4% (95% CI: 55.0–61.7%) in 1981–1985 to 91.3% (95% CI: 90.5–92.1%) in 2011–2015. Prostate cancer mortality rates decreased from 1990 onwards (1990–2006: APC −1.7, 95% CI −2.1, −1.2; 2006–2017: APC −3.8, 95% CI −4.4, −3.1).ConclusionsOverall, there was a decrease in the incidence rate of localized prostate cancer after 2008, an increase in survival over time and a decrease in the mortality rate since the 1990s. This seems to indicate that the more conservative use of PSA screening tests in clinical practice since 2008 has not had a negative impact on population-wide prostate cancer outcomes.