良性前列腺增生及前列腺癌的ADC值与PAP、P504S、PSA表达的相关性研究

目的：探讨良性前列腺增生和前列腺癌的ADC值与前列腺相关标志物PAP、P504S、PSA表达的关系。方法收集经病理证实的65例前列腺疾病患者,其中良性前列腺增生30例,前列腺癌35例。病理检查前3个月内均行前列腺MRI、DWI检查,采用单次激发EPI序列,b值为0 s/mm2和800 s/mm2,并采用免疫组化检测组织标本中PAP、P504S、PSA的表达,分析ADC值与PAP、P504S、PSA表达的关系。结果良性前列腺增生和前列腺癌的ADC值分别为（1.73±0.21）×10-3 mm2/s和（1.34±0.15）×10-3 mm2/s,差异具有统计学意义（t=8.545,P=0.000）。PAP和PSA在良性前列腺增生和前列腺癌中均表达,差异无统计学意义（P均＞0.05）,P504S在前列腺癌中的表达显著高于良性增生（Z=-7.055,P=0.000）,双变量相关分析显示ADC值与P504S的表达呈显著负相（Spearman's相关系数r=-0.654,P=0.000）;结论 PAP和PSA不能区别前列腺良恶性病变;P504S可以作为前列腺癌标志物;ADC值可以定量评价良性前列腺增生和前列腺癌,且与P504S存在负相关,可以作为前列腺良恶性病变MRI诊断的参考指标。     

表面增强激光解析电离飞行时间质谱技术在前列腺癌蛋白质组研究中的应用

目的应用表面增强激光解析电离飞行时间质谱（SELDI—TOF—MS）和蛋白质芯片技术分析前列腺癌（PCa）差异蛋白表达及其与病理分级和临床分期的关系,初步探讨雄激素难治性前列腺癌（HRPC）的发病机制。方法以病理确诊的PCa和良性前列腺增生（BPH）各45例,另以HRPC与激素依赖性前列腺癌（ADPC）各21例患者血清为研究对象,采用SELDI—TOF-MS固相金属亲和芯片技术检测血清的蛋白表达图谱,用BiomarkerWizard软件分析差异蛋白。结果在PCa和BPH患者血清中检测到9个差异蛋白（P〈0．01）,各差异蛋白在不同病理分级间表达差异有统计学意义。HRPC与ADPC有6个血清蛋白表达,差异有统计学意义（P〈0．05）。结论通过SELDI—TOF—MS蛋白质芯片技术检测PCa的标志蛋白可以提高PCa诊断的敏感度和特异度;差异蛋白在PCa不同病理分级间表达差别可能与PCa分化、肿瘤侵袭生长有关。HRPC与ADPC患者血清的差异蛋白可能在ADPC向HRPC转变过程中发挥着重要作用,检测差异蛋白可以明确诊断,评估预后,指导治疗。     

前列腺癌的差异蛋白及其临床意义的研究

目的应用表面增强激光解析电离飞行时间质谱（SELDI-TOF-MS）和蛋白质芯片技术,探讨前列腺癌差异蛋白表达及其与病理分级和临床分期的关系。方法以病理确诊的前列腺癌和良性前列腺增生各45例为研究对象,采用SELDI-TOF-MS蛋白质芯片技术检测血清的蛋白表达图谱,用Biomarker Wizard软件分析差异蛋白,对所得差异蛋白进一步分析。结果在前列腺癌和良性前列腺增生患者血清中检测到9个差异蛋白（P〈0.01）,前列腺癌患者血清差异蛋白7个高表达,2个低表达。各差异蛋白在不同病理分级间表达差异有统计学意义。结论通过SELDI-TOF-MS蛋白质芯片技术检测前列腺癌的特异蛋白可以提高前列腺癌诊断的敏感性和特异性。差异蛋白在前列腺癌不同病理分级间表达差别可能与前列腺癌分化、肿瘤侵袭生长有关,检测差异蛋白可以明确诊断,评估预后,指导治疗。     

胸科手术中不同通气方式的患者血清中蛋白质组学的研究

目的应用同位素标记的绝对和相对定量（isobaric tags for relative and absolute quantitation，iTRAQ）技术筛选并鉴定胸科手术中分别采用单肺通气和双肺通气的患者血清中差异表达的蛋白质。方法收集胸科手术中采用单肺通气和双肺通气的患者血清，每组各10例，将每一组血清等量混合后应用多重免疫亲和层析柱（MARS）去除血清中的高丰度蛋白，样本经iTRAQ标记和液相色谱分离后，用质谱仪进行鉴定和相对定量分析。结果经质谱鉴定共获得189种蛋白质，其中差异表达的蛋白质有42种（上调或下调20％）。单肺通气组与双肺通气组比较，有33种蛋白质表达上调，9种表达下调。结论iTRAQ技术能够快速、有效地进行差异蛋白质组学的研究，能筛选出多种与单肺通气肺损伤相关的生物标记蛋白，为进一步研究单肺通气肺损伤发生的机制提供实验依据。     

前列腺特异膜抗原对前列腺疾病的临床诊断意义

目的评价血清中前列腺特异膜抗原（PSMA）浓度对前列腺疾病的辅助诊断意义。方法采用Western印迹分析检测患者血清中PSMA的浓度,前列腺特异抗原（PSA）检测采用通用的免疫化学发光法检测。分析二者在不同分组中的浓度差异及相关性。结果前列腺癌患者的血清中PSMA浓度显著高于正常人群,良性前列腺增生和前列腺炎的患者则低于正常人群,而PSA浓度无论是前列腺癌还是前列腺良性病变均高于正常人。结论前列腺特异膜抗原浓度可以作为区分前列腺癌和良性前列腺增生的辅助诊断标志物。     

前列腺特异性膜抗原在前列腺癌患者外周血和组织中的表达及意义

目的探讨前列腺特异性膜抗原（PSMA）在前列腺癌患者（PCa）外周血和组织中的表达及其与肿瘤病理分级和临床分期之间的关系。方法采用RT-PCR方法检测前列腺特异性膜抗原（PSMA）在前列腺癌和良性增生患者外周血清中的表达;采用免疫组化法观察PSMA在前列腺不同病变组织中的表达。前列腺癌28例,前列腺上皮内瘤（PIN）7例,良性前列腺增生（BPH）30例。结果血清学检测显示PSMA mRNA在前列腺癌和良性病变组（包括PIN和BPH）患者外周血中阳性率分别为67.9%和8.1%,两者差异具有显著性（P〈0.01）。在局限性癌、局部进展性癌和远处转移癌患者外周血肿瘤细胞中,PSMA mRNA的阳性率分别为58.3%、66.7%和85.7%,随前列腺癌临床分期的进展而逐渐递增（P〈0.05）。在高分化、中分化和低分化前列腺癌中,PSMA mRNA的阳性率分别为87.5%、62.5%和50%,肿瘤分化越差,其阳性率越低（P〈0.05）。组织学检测显示PSMA在PCa、PIN、BPH三种不同前列腺病变组织中的阳性率分别为60.7%、28.6%和20.0%（P〈0.05）,在高、中、低分化前列腺癌组织中PSMA的阳性率分别为100.0%、50.0%和25.0%,与肿瘤Gleason评分之间呈负相关（P〈0.05）。在局限性癌、局部进展性癌和远处转移癌患者肿瘤组织中,PSMA的阳性率分别为58.3%（7/12）、77.8%（7/9）和42.9%（3/7）（P〉0.05）。结论PSMA在前列腺癌组织中明显高表达,并且表达量与前列腺癌临床分期和分化程度（组织学分级）密切相关;检测PSMA可能对前列腺癌诊断、治疗方案的选择及预后评估具有重要价值。     

前列腺癌组织卵泡刺激素受体表达临床意义的研究

目的:探讨卵泡刺激素受体在前列腺癌组织中的表达及其临床意义.方法:采用SP免疫组化方法,分析12例正常前列腺(NP)、14例前列腺增生(BPH)、45例前列腺癌(PCa)标本中FSHR的阳性表达情况和45例PCa标本中雄激素受体(AR)的表达情况.结果:NP组仅2例FSHR表达阳性,BPH组4例表达阳性,PCa组38例表达阳性,NP组与BPH组比较差异无统计学意义,BPH组与PCa组比较差异有统计学意义;FSHR在PCa组的表达程度与不同病理分级、临床分期和Gleason分级呈正相关.结论:FSHR在前列腺癌组织中的表达明显强于良性增生和正常的前列腺组织;FSHR与前列腺癌的发生、发展、转移等生物学行为有密切关系.     

海南地区Gleason评分≥7分的前列腺癌患者血清PSA和睾酮水平与预后相关性探讨

目的:分析海南地区Gleason评分≥7分的前列腺癌（prostatic cancer,PCa）患者血清前列腺特异性抗原(prostate specific antigen,PSA)和总睾酮（total testosterone,TT）水平与5年总生存率的相关性。方法:回顾性分析2009年01月至2019年12月我院收治的前列腺癌患者106例作为PCa组,选取同期良性前列腺增生症（benign prostatic hyperplasia,BPH）患者120例作为BPH组,比较两组患者临床资料、血清PSA、TT水平;再根据PCa组患者5年生存情况分为生存组（n=81）和死亡组（n=25）,比较两组患者临床资料、Gleason评分、血清PSA、TT水平;采用多因素COX回归分析影响前列腺癌患者预后的独立危险因素;绘制受试者工作特征曲线（receiver operating characteristic curve,ROC）,分析血清PSA、TT水平早期评估前列腺癌患者预后的预测价值;采用Spearman相关性模型分析血清PSA、TT水平与病理Gleason评分的相关性。结果:PCa组患者年龄、前列腺体积、血清PSA水平高于BPH组,血清TT水平低于BPH组,差异具有统计学意义（P＜0.05）;生存组患者Gleason评分、血清PSA水平、骨转移发生率、TNM分期低于死亡组,血清TT水平高于死亡组,差异具有统计学意义（P＜0.05）;Spearman相关性分析显示,血清PSA水平与病理Gleason评分呈正相关（r=0.634,P＜0.05）,血清TT水平与病理Gleason评分呈负相关（r=-0.755,P＜0.05）;多因素COX回归分析显示,高PSA水平（HR=1.352）、高Gleason评分（HR=4.576）、高TNM分期(HR=2.937)和骨转移（HR=1.258）是前列腺癌患者预后的独立危险因素（P＜0.05）,高TT水平（HR=0.063）是前列腺癌患者预后的保护因素（P＜0.05）;ROC曲线显示,血清PSA、TT水平及两者联合早期预测前列腺癌患者预后的曲线下面积（area under curve,AUC）为0.811、0.887和0.934,敏感度为88.00%、96.00%和92.00%,特异度为68.73%、72.84%和82.72%,截点值分别为21.51 ng/mL和3.74 ng/mL。结论:前列腺癌患者血清PSA、TT水平可作为早期评估患者预后的重要指标,其与病理Gleason评分存在高度相关性。     

VEGF在前列腺癌中的表达及与肿瘤MVD的关系

目的:研究前列腺癌组织中的血管内皮生长因子（VEGF）表达与前列腺癌肿瘤微血管密度（MVD）的关系。方法:选取81例确诊前列腺癌患者及良性前列腺增生患者52例。采用免疫组化法进行染色,观察两种组织中VEGF、MVD的表达情况,并分析VEGF与前列腺癌患者的临床病理特征关系及与MVD之间的关系。结果:前列腺癌组织中VEGF阳性表达率（69.14%）显著的高于前列腺良性增生组（28.85%）,差异具有统计学意义（P<0.05）。前列腺癌组织中MVD计数为（36.7±8.2）显著高于前列腺良性增生组（19.3±5.8）,差异具有统计学意义（P<0.05）。前列腺癌组织中VEGF表达阳性率与患者的TNM分期、淋巴结转移、分化程度具有显著关联（P<0.05）。VEGF表达阳性的癌组织中MVD（40.3±7.5）显著多于VEGF表达阴性的癌组织（28.7±6.1）,差异具有统计学意义（P<0.05）。结论:前列腺癌组织中VEGF高表达,MVD生成增多,VEGF与患者的临床病理特征具有一定的关系,VEGF阳性表达患者的MVD增生水平越高。     

弥散加权成像对鉴别前列腺癌和前列腺增生的意义

目的：探讨前列腺弥散加权成像测得的ADC值结合常规MRI对鉴别前列腺癌和前列腺增生的价值。方法：选择前列腺增生病人15例,前列腺癌病人10例,分析采用b值为1000的ADC图及常规MR图像,结合常规MRI在ADC图上选取感兴趣区测量前列腺癌（PCa）、前列腺增生（BPH）外围带（PZ）和前列腺增生中央带（CG）的ADC值。比较差异性并分析重叠情况。结果：前列腺增生表现为信号不均,增生结节有的为T2WI高信号,有的为T2WI低信号,前列腺癌有时与增生结节难以鉴别。PCa的ADC值（0.67±0.06）×10-3mm2/s,前列腺增生外围带（PZ）的ADC值（1.52±0.18）×10-3mm2/s,前列腺增生中央带（CG）的ADC值（1.05±0.25）×10-3mm2/s,BPH的PZ与PCa及BPH的CG与PCa均有显著差异,BPH的PZ与PCa间无重叠,BPH的CG与PCa间有少量重叠。结论：DWI对鉴别前列腺癌和前列腺增生有意义,但由于分辨力的限制,测量ADC值时要参照常规MRI以使选取的区域更准确。     

Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis

Although serum prostate specific antigen (PSA) is a well-established diagnostic tool for prostate cancer (PCa) detection, the definitive diagnosis of PCa is based on the information contained in prostate needle biopsy (PNBX) specimens. To define the proteomic features of PNBX specimens to identify candidate biomarkers for PCa, PNBX specimens from patients with PCa or benign prostatic hyperplasia (BPH) were subjected to comparative proteomic analysis. 2-DE revealed that 52 protein spots exhibited statistically significantly changes among PCa and BPH groups. Interesting spots were identified by MALDI-TOF-MS/MS. The 2 most notable groups of proteins identified included latent androgen receptor coregulators [FLNA(7-15) and FKBP4] and enzymes involved in mitochondrial fatty acid beta-oxidation (DCI and ECHS1). An imbalance in the expression of peroxiredoxin subtypes was noted in PCa specimens. Furthermore, different post-translationally modified isoforms of HSP27 and HSP70.1 were identified. Importantly, changes in FLNA(7-15), FKBP4, and PRDX4 expression were confirmed by immunoblot analyses. Our results suggest that a proteomics-based approach is useful for developing a more complete picture of the protein profile of PNBX specimen. The proteins identified by this approach may be useful molecular targets for PCa diagnostics and therapeutics.     

DCE-MRI联合血清sE-cadherin、AGR2检测诊断前列腺癌的临床价值

目的:探讨动态增强磁共振（dynamic contrast enhanced MRI,DCE-MRI）扫描联合血清上皮钙黏蛋白（soluble E-cadherin,sE-cadherin）、前梯度蛋白2（anterior gradient-2,AGR2）对前列腺癌（prostatic cancer,PCa）的诊断价值。方法:选择2015年02月至2018年02月我院收治的行前列腺穿刺活检经病理确认诊断为前列腺癌（PCa）患者98例记为PCa组,104例前列腺增生（BPH）患者记为BPH组,同时以同期的92例在我院体检的健康男性为对照组。比较PCa组和BPH组的DCE-MRI容量转移常数（Ktrans）、速率常数（Kep）、血管外细胞外间隙容积比（Ve）、血浆内对比剂容积分数（Vp）以及三组的血清sE-cadherin、AGR2情况。以Logistics回归模型拟合联合诊断,并通过受试者工作特征（receiver operating characteristic,ROC）曲线分析各指标诊断价值。结果:PCa组的血清sE-cadherin、AGR2水平均高于BPH组和对照组（P＜0.05）,且BPH组高于对照组（P＜0.05）。PCa组的Ktrans、Kep、Ve均高于BPH组（P＜0.05）;两组的Vp比较无统计学差异（P＞0.05）。联合诊断的灵敏度82.65%也显著高于Ktrans（60.20%）、Kep（66.33%）、Ve（65.31%）、sE-cadherin（63.27%）、AGR2（58.16%）单独检测,差异均具有统计学意义（P＜0.05）。联合检测ROC曲线下面积0.867（95%CI:0.826~0.908）,高于Ktrans 0.650（95%CI:0.577~0.722）、Kep 0.693（95%CI:0.621~0.764）、Ve 0.826（95%CI:0.776~0.876）、sE-cadherin 0.807（95%CI:0.753~0.861）、AGR2 0.759（95%CI:0.701~0.817）分别单独检测。结论:采用 DCE-MRI检查血管渗透性参数和血清sE-cadherin及AGR2水平对于前列腺癌诊断具有重要意义,且三者联合检测能够提高诊断的灵敏度和准确度,为前列腺癌的临床诊断提供新的检测依据。     

Predictive Value of the Platelet-To-Lymphocyte Ratio in Diagnosis of Prostate Cancer

Purpose: To predict prostatic carcinoma using a logistic regression model on prebiopsy peripheral bloodsamples. Materials and Methods: Data of a total of 873 patients who consulted Urology Outpatient Clinics of FatihSultan Mehmet Training and Research Hospital between February 2008 and April 2014 scheduled for prostatebiopsy were screened retrospectively. PSA levels, prostate volumes, prebiopsy whole blood cell counts, neutrophiland platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), biopsy resultsand Gleason scores in patients who had established diagnosis of prostate cancer (PCa) were evaluated. Results:This study was performed on a total of 873 cases, with an age range 48-76 years, divided into three groups asfor biopsy results. with diagnoses of benign prostatic hyperplasia (BPH) (n=304, 34.8 %), PCa (n=265, 30.4 %)and histological prostatitis (n=304; 34.8 %). Intra- and intergroup comparative evaluations were performed.White blood cell and neutrophil counts in the histological prostatitis group were significantly higher than thoseof the BPH and PCa groups (p=0.001; p=0.004; p<0.01). A statistically significant intergroup difference wasfound for PLR (p=0.041; p<0.05) but not lymphocyte count (p>0.05). According to pairwise comparisons, PLRwere significantly higher in the PCa group relative to BPH group (p=0.018, p<0.05, respectively). Though notstatistically significant, higher PLR in cases with PCa in comparison with the prostatitis group was remarkable(p=0.067, and p>0.05, respectively). Conclusions: Meta-analyses showed that in patients with PSA levels over4 ng/ml, positive predictive value of PSA is only 25 percent. Therefore, novel markers which can both detectclinically significant prostate cancer, and also prevent unnecessary biopsies are needed. Relevant to this issuein addition to PSA density, velocity, and PCA3, various markers have been analyzed. In the present study, PLRw ere found to be the additional predictor of prostatic carcinoma.     

Identification of novel biomarkers differentially expressed between African-American and Caucasian-American prostate cancer patients

Prostate cancer (PCa) incidence and mortality rate vary among racial and ethnic groups with the highest occurrence in African American (AA) men who have mortality rates twice that of Caucasians (CA). In this study, we focused on differential expression of proteins in AA prostate cancer compared to CA using Protein Pathway Array Analysis (PPAA), in order to identify protein biomarkers associated with PCa racial disparity. Fresh frozen prostate samples (n=90) obtained from radical prostatectomy specimens with PCa, including 25 AA tumor, 21 AA benign, 23 CA tumor, 21 CA benign samples were analyzed. A total of 286 proteins and phosphoproteins were assessed using PPAA. By PPAA analysis, 33 proteins were found to be significantly differentially expressed in tumor tissue (n=48, including both CA and AA) in comparison to benign tissue (n=42). We further compared protein expression levels between AA and CA tumor groups and found that 3 proteins were differentially expressed (P<0.05 and q<5%). Aurora was found to be significantly increased in AA tumors, while Cyclin D1 and HNF-3a proteins were downregulated in AA tumors. Predicted risk score was significantly different between AA and CA ethnic groups using logistic regression analysis. In conclusion, we identified Aurora, Cyclin D1 and HNF-3a proteins as being differentially expressed between AA and CA in PCa tissue. Our study suggests that these proteins might be involved in different pathways that lead to aggressive PCa behavior in AA patients, potentially serving as biomarkers for the PCa racial disparity.     

Matrix metalloproteinases 1 and 3, tissue inhibitor of metalloproteinase-1 and the complex of metalloproteinase-1/tissue inhibitor in plasma of patients with prostate cancer

We analyzed blood plasma concentrations of matrix metalloproteinase-1 and -3 (MMP-1; MMP-3), the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the complex MMP-1/TIMP-1, and looked for any correlation with prostate cancer stage. These components were measured by ELISA tests specific for these proteins in healthy male controls (n = 35), and in patients with benign prostatic hyperplasia (BPH; n = 29), with prostate cancer (PCa) without metastasis (T2,3pN0M0; n = 29) and with PCa with metastatic disease (T2,3,4pN1,2M1; n = 18). Mean values of MMP-1 and of the complex MMP-1/TIMP-1 were not different among the 4 groups studied. The mean MMP-3 and especially TIMP-1 concentrations were significantly higher in PCa patients with metastases compared with controls, BPH and PCa patients without metastases. Ten of these 18 patients had TIMP-1 concentrations higher than the upper reference limit. TIMP-1 concentrations were correlated with staging but not with grading. Our results point towards plasma TIMP-1 concentration as a potential marker of malignant progression of PCa. Int. J. Cancer 74:220-223, 1997. © 1997 Wiley-Liss, Inc.     

Classical and Alternative Nuclear Factor-κB Pathways: A Comparison among Normal Prostate, Benign Prostate Hyperplasia and Prostate Cancer

Nuclear factor-κB (NF-κB) is controlled by the classical and alternative NF-κB pathways, the role of which in prostate cancer (PCa) is not clearly defined. To provide this missing translational link, we compared the classical and alternative NF-κB pathways in normal prostate, benign prostate hyperplasia (BPH) and PCa. Prostate specimens were divided into three groups: group A, PCa (n?=?68); group B, BPH (n?=?60); and group C, normal prostates (n?=?15). The gene expression levels of NF-κB1 and NF-κB2 were determined by real-time quantitative RT-PCR. Additionally, we analyzed the expression and sub-cellular localization of phosphorylated P50 (p-P50) and phosphorylated P52 (p-P52) proteins by immunohistochemical staining. Furthermore, associations were made between NF-κB pathway proteins and patients' prognosis. Compared with BPH and normal prostate tissues, the expression of NF-κB1 gene was differentially down-regulated by >1.5-fold, whereas NF-κB2 gene was differentially up-regulated by >2-fold in PCa tissues. The proportion of p-P50 positive patients in group A (26.5%) was significantly lower than in group B (88.3%, p?=?0.005) and C (100%, p?=?0.002). The proportion of p-P52 positive patients in group A (42.6%) was significantly higher than in group B (11.7%, p?=?0.009) and C (6.7%, p?=?0.008). Comparison of the survival curves in group A according to p-P52 expression showed a significant difference between positive and negative patients. The p-P52 positive patients showed worse prognosis (p?=?0.019). Our findings suggest for the first time that the classical and alternative NF-κB pathways have an important role in PCa. p-P52 might be a predictor of poor prognosis for PCa.     

前列腺特异性抗原的检测对前列腺癌及前列腺增生的诊断意义

目的　探讨血清总前列腺特异性抗原 (t PSA)、游离PSA (f PSA)、PSA密度 (PSAD )及其f PSA/t PSA比值对前列腺癌 (PCa)及前列腺增生 (BPH )的诊断价值。方法　采用酶联免疫分析方法 (ELISA )检测未经治疗的 62例BPH患者和 2 4例PCa患者血清f PSA、t PSA水平 ,并计算f PSA/t PSA值和PSAD ,对检测结果进行统计学处理。结果　BPH组与PCa组的f PSA、t PSA水平均明显高于对照组 (P <0 .0 1) ;前列腺癌组的f PSA /t PSA值明显小于对照组及前列腺癌增生组 (P <0 .0 1) ;PCa组PSAD明显大于对照组和BPH组 (P <0 .0 1)。结论　检测f PSA/t PSA和PSAD比单一检测f PSA、t PSA可显著提高对PCa诊断的特异性及符合率 ,对前列腺体积较大的BPH和PCa患者 ,检测PSAD更有意义