前列腺特异性抗原及其相关标志物在前列腺癌早期诊断中的研究进展

前列腺特异性抗原（PSA）是一项有效的预测前列腺癌的肿瘤标志物,但却不是肿瘤特异性的标志物.为了提高其特异性和敏感性,早期发现前列腺癌,多种与PSA相关的概念相继提出,本文就PSA及其相关标志物在前列腺癌早期诊断作一综述.     

PSA动力学在前列腺癌的诊断与预后评估中的意义

合适的肿瘤标志物对于恶性肿瘤的早期诊断和预后评估十分重要。自1960年前列腺特异性抗原(PSA)被发现以来,其已成为前列腺癌诊断和预后评估的主要肿瘤标志物[1]。大量的临床实践证明,PSA仍有很多不足之处,如特异性较差。在前列腺增生症和前列腺炎患者的血清中PSA     

前列腺癌生物标志物筛查的临床研究现状

肿瘤的生物标志物研究对肿瘤的早期诊断和治疗有重要意义。虽然前列腺特异性抗原(PSA)用于临床前列腺癌的筛查和治疗效果评价已经20余年,但是其效果并不能完全让人满意。随着对前列腺癌研究的深入,目前已经发现了多种前列腺癌的生物标志物。本文就前列腺癌生物标志物筛查的临床研究进展进行综述。     

前列腺癌诊断标志物研究现状

随着前列腺特异性抗原（PSA）的广泛应用,前列腺癌（PCa）患者及前列腺穿刺活检数量明显增加,但PSA特异性及对前列腺癌的诊断价值仍然存在争议。目前已出现更多诊断PCa的DNA、RNA和抗原标志物,本文将对与PCa诊断相关的肿瘤标志物研究现状作一简要概述。     

血清良性PSA与血清PSA前体在前列腺癌早期诊断中的临床应用研究进展

近年来,前列腺癌发病率在我国呈显著增长趋势。由于前列腺癌生物学行为具有特殊性,研究用于前列腺癌早期诊断的新的标志物已成为泌尿外科领域一个越来越重要的课题。继前列腺特异性抗原(PSA)、PSA密度(PSAD)、游离PSA与总PSA比值(f/tPSA)、cPSA与tPSA比值(c/tPSA)及cPSA移行带指数(cPSA-Tz)等瘤标之后,血清良性PSA(BPSA)与血清PSA前体(proPSA)已成为一个新的研究热点。目前血清良性PSA(BPSA)与血清PSA前体(proPSA)的临床应用尚处于研究阶段,却有望成为特异性和敏感性更高的前列腺癌标志物。本文就其最新研究成果作一综述。     

前列腺癌抗原3联合检测在前列腺癌早期诊断中的作用

前列腺癌（PCa）是欧美国家发病率最高的男性恶性肿瘤,随着我国居民生活水平的提高,前列腺癌的发病率不断增加。目前,前列腺癌患者的筛选主要依靠血清前列腺特异性抗原（PSA）检测,PSA检测具有较高的敏感度,许多前列腺癌患者可以通过这一手段被检出,但PSA检测也存在较低特异性的特点,这使得探索更具诊断价值的前列腺癌肿瘤标志物成为前列腺癌早期诊断发展的趋势。前列腺癌抗原3(PCA3)是近年来发现的较有临床应用价值的前列腺癌肿瘤标记物之一,本文就PCA3与其他肿瘤标志物联合检测在前列腺癌诊断中的作用作一综述。     

PSA衍生指标诊断前列腺癌的研究进展

血清前列腺特异性抗原(PSA)是目前应用最为广泛的前列腺癌生物标志物,可以有效筛选出前列腺癌高危人群,监测病情变化。但是血清总PSA(tPSA)的特异性不强,容易造成误诊。近年来,国内外研究人员开发出一系列PSA衍生指标,与tPSA以及其他诊断方法(如MRI、超声、直肠指检结果和其他肿瘤标志物)联合应用能够进一步提高前列腺癌的早期诊断准确率,并可用于评估肿瘤恶性程度、侵袭性、术后生化复发以及帮助制定前列腺穿刺活检决策等,具有广阔的研究前景。本文就PSA衍生指标诊断前列腺癌的最新研究进展进行综述。     

血清良性PSA与血清PSA前体在前列腺癌早期诊断中的临床应用研究进展

近年来。前列腺癌发病率在我国呈显著增长趋势。由于前列腺癌生物学行为具有特殊性，研究用于前列腺癌早期诊断的新的标志物已成为泌尿外科领域一个越来越重要的课题。继前列腺特异性抗原(PSA)、PSA密度(PSAD)、游离PSA与总PSA比值(f／tPSA)、cPSA与tPSA比值(c／tPSA)cPSA移行带指数(cPSA-Tz)等瘤标之后。血清良性PSA(BPSA)与血清PSA前体(proPSA)已成为一个新的研究热点。目前血清良性PSA(BPSA)与血清PSA前体(proPSA)的临床应用尚处于研究阶段，却有望成为特异性和敏感性更高的前列腺癌标志物。本文就其最新研究成果作一综述。     

前列腺癌诊断标志物的研究进展

前列腺癌是男性生殖系统肿瘤的常见病,在欧美等国家前列腺癌是男性发病率最高的恶性肿瘤,占癌症死亡率的第二位[1].随着老龄化人口的发展及诊疗水平的不断提高,前列腺癌在中国的发病率及检出率也呈显著增长趋势,是威胁老年男性健康的一个重要因素[2].目前前列腺癌实验室早期诊断指标主要是血清前列腺特异性抗原(PSA),但是血清PSA作为前列腺特异性而非前列腺癌特异性标志物,在有关前列腺各种检查(直肠指诊和经直肠超声)及非肿瘤状态下(如良性前列腺增生、前列腺炎)也有表达.临床上将PSA＞4 ng/ml作为前列腺癌诊断的临界值,但是当PSA值在4～10 ng/ml 时,前列腺癌的检出率仅在25%左右,活检阴性率占70%～80%,阴性的活检结果并不能完全排除恶性肿瘤存在的可能性[3].因此寻找敏感性、特异性高的生物标志物仍是目前研究的重点,本文就近几年研究较为热点的几种标志物予以综述.     

核酸检测在前列腺癌诊断中的研究现状

前列腺特异性抗原(PSA)作为诊断前列腺癌最常用的标志物,提高了早期前列腺癌的发现率,但其特异性不高,造成PSA灰区的患者过度诊断和治疗。随着大量分子检测技术的涌现,核酸检测已成为能够显著提高前列腺癌诊断率的方法之一。DNA中的融合基因TMPRSS2-ERG、PTEN丢失、线粒体DNA过量表达以及其3.4kb丢失在前列腺癌发生和发展中起到重要作用,一种被称为ConfirmMDX用于检测表观遗传现象的技术显著提高了前列腺癌诊断特异性。RNA中的前列腺特异性抗原3、微小RNA、肺腺癌转录相关转移物1在诊断前列腺癌中的价值也备受关注。本文对此进行了综述。     

Molecular diagnosis of prostate cancer

The diagnosis, staging, and management of prostate cancer as we know it today is greatly dependent on our ability to measure serum prostate-specific antigen (PSA) concentration. Nevertheless, because serum PSA concentration, particularly when less than 10 ng/mL, reflects the presence of benign prostatic hyperplasia more often than cancer, there is a clear need for more specific prostate cancer markers. The most promising new markers for prostate cancer are the various molecular forms of free PSA. Mass spectrometry also is emerging as a potential tool in prostate cancer screening. Because it is unlikely that any one marker will have 100% sensitivity and specificity, as new serum markers are tested, nomograms that incorporate multiple independently predictive parameters for the detection of prostate cancer will become indispensable in our efforts to improve prostate cancer screening.     

前列腺癌干细胞标志物研究进展

前列腺癌是严重影响男性健康的恶性疾病,其发生、发展机理仍未完全明了。近年来前列腺癌干细胞的研究取得了多方面的进展,研究材料涉及人前列腺癌组织、前列腺癌细胞系,以及鼠前列腺癌模型。前列腺癌干细胞的研究为前列腺癌的发生和发展提出了一个全新的理念,对于前列腺癌的治疗具有积极意义。本文就近些年来在前列腺癌干细胞研究中应用于分离鉴定前列腺癌干细胞的标志物情况进行综述。     

Biochemical staging of prostate cancer

PSA continues to be one of the most effective and widely used cancer screening tools available. Its popularity in prostate cancer screening, however, has eroded its usefulness in the staging of this disease. As more men are screened every year on a routine basis with DRE and PSA, the average PSA at diagnosis has drifted down to well below 10 ng/mL in many centers, including ours. This trend is likely to accelerate, as a PSA cut off for prompting biopsy of the prostate of 2.5 ng/mL gains more widespread acceptance. The recent realization that, at these levels, serum PSA is more reflective of the presence of BPH than of the extent of cancer and, therefore, does not provide additional staging information, has renewed the search for new biochemical markers that are capable of predicting prostate cancer stage and prognosis. Because of the heterogeneity of this disease, it is unlikely that a single biochemical marker that is capable of accurately staging all prostate cancer patients will be found. For this reason, nomograms that are capable of integrating various parameters to predict stage and prognosis will remain indispensable. As new biochemical markers that provide independent predictive information about stage or prognosis are identified, they can be incorporated into currently available nomograms. Of the biochemical markers discussed in this article, IL-6sR and TGF-beta1 are the most promising. By incorporating them into a preoperative nomogram designed to predict PSA recurrence, we found that they improved the ability to predict biochemical recurrence by a statistically and clinically significant margin. The ability to stage prostate cancer and predict response to therapy has improved dramatically over the last 3 decades. Nevertheless, there is still a need for new biochemical markers that will improve the ability to predict an individual patient's stage and response to therapy. Incorporating these new markers into nomograms will enhance the ability to provide optimal care for each prostate cancer patient.     

Prostate cancer screening markers

Prostate cancer is the most frequent new cancer diagnosis in the Western world. Prostate-specific antigen (PSA) was shown to be an adequate tool in prostate cancer screening. However, in men with a PSA level between 4.0 and 10 ng/ml its predictive value is low. PSA serum levels are poorly correlated with grade and stage of prostate cancer, and clinically significant prostate cancers have been found in patients with serum PSA levels lower than 4.0 ng/ml. The widespread use of PSA screening programs led to over-diagnosis and unnecessary biopsies. Consequently, there is a need for new instruments that are likely to improve the specificity of serum PSA levels between 4.0 and 10 ng/ml and the screening for prostate cancer in subjects with low PSA. Potential biomarkers related to conventional PSA, such as free PSA, PSA density, PSA velocity and complexed PSA, intact PSA, nicked PSA, benign PSA and pro PSA, as well as insulin-like growth factor 1 and its binding protein, and human glandular kallikrein 2 are reviewed. Promising urinary markers for the early detection of prostate cancer, such as glutathione-S transferase P1 gene (GSTP-1), 8-hydroxydeoxyguanosine (8-OHdG), differential display code 3 (DD3), uPM3, and telomerase, which have been described during the last years are reviewed in this article. The advantages and limitations of screening markers for prostate cancer are discussed.     

Molecular detection of prostate cancer: a role for GSTP1 hypermethylation

OBJECTIVE: Prostate cancer is a leading cause of cancer-related mortality and morbidity in Western world. Curative treatment is feasible provided the disease is diagnosed in its earliest stages, but current screening methodologies are characterized by low specificity. DNA-based markers are a class of new and promising tools for cancer detection. Promoter hypermethylation is a common epigenetic alteration affecting cancer-related genes. METHODS: We critically reviewed the most relevant reports on prostate cancer detection using DNA methylation analysis in prostate tissue and body fluids. RESULTS: The epigenetic silencing of the glutathione-S-transferase P1 (GSTP1) gene is the most common (>90%) genetic alteration so far reported in prostate cancer. Methylation-specific PCR (MSP) methods allowed for the successful detection of GSTP1 methylation in body fluids (serum, plasma, urine, and ejaculates) from prostate cancer patients. In addition, the development of highly specific quantitative MSP assays augmented standard histopathology for the diagnosis of prostate cancer in tissue biopsies, accurately distinguishing benign from malignant prostate lesions. CONCLUSIONS: Further advances in the epigenetic characterization of prostate cancer are likely to yield powerful tools for patient diagnosis and management.     

PSA and hK2 in the diagnosis of prostate cancer

Serum markers for prostate carcinoma are widely applied for the purpose of early detection of cancer and the differentiation between benign and malignant disease, for the pre-treatment staging of detected prostatic cancers, and for the monitoring of prostate cancer after curative or palliative therapies. Since its discovery in 1979, serum PSA has been the most powerful marker of prostate cancer, but, when used alone, PSA is not sufficiently sensitive or specific to consider it an ideal tool for the early detection or staging of prostate cancer. To optimize the use of PSA, the concepts of PSA velocity, PSA density, and age-related PSA values were developed. Moreover, the molecular forms of PSA, especially the percentage of free PSA, seem to be useful tools for the detection of prostate cancer in men with slightly elevated total PSA. Human kallikrein 2 (hK2), a serine protease closely related to PSA that also is expressed predominantly in the prostate, is a new complementary marker to PSA for early detection of prostate cancer. In this review, we examine PSA testing and its effectiveness in the diagnosis of prostate cancer. Further, we also evaluate recent literature regarding the use of hk2.     

Mechanisms of Disease: biomarkers and molecular targets from microarray gene expression studies in prostate cancer

Molecular biomarkers can serve as useful diagnostic markers, as prognostic markers for predicting clinical behavior, or as targets for new therapeutic strategies. Application of expression microarray technology, which allows the expression of all or most of the genes in the human genome to be analyzed simultaneously, has dramatically enhanced the discovery of prostate cancer biomarkers. The diagnostic markers identified include AMACR (alpha-methylacyl CoA racemase), a protein that has already been translated into clinical use as an aid in distinguishing prostate cancer from benign disease. Individual genes, such as the polycomb gene EZH2 whose expression indicates poor survival, have been identified. The power of microarray technology is that it has allowed the identification of gene signatures (each composed of multiple genes) that might provide improved prediction of clinical outcomes in human prostate cancer. The development of a new method for analyzing expression microarray data, called COPA, has led to the discovery of TMPRSS2-ERG gene fusion involvement in the development of prostate cancer, while expression analysis of castration-resistant prostate cancer has suggested the use of novel therapeutic approaches for advanced disease. Despite these successes, there are limitations in the application of microarray technology to prostate cancer; for example, unlike with other cancers, this approach has failed to provide a consistent unsupervised classification of the disease. Overcoming the reasons for these failures represents a major challenge for future research endeavors.     

Prostate cell cultures as in vitro models for the study of normal stem cells and cancer stem cells

Current existing therapies for prostate cancer eradicate the majority of cells within a tumor. However, most patients with advanced cancer still progress to androgen-independent metastatic disease that remains essentially incurable by current treatment strategies. Recent evidence has shown that cancer stem cells (CSCs) are a subset of the tumor cells that are responsible for initiating and maintaining the disease. Understanding normal stem cells and CSCs may provide insight into the origin of and new therapeutics for prostate cancer. Normal stem cells and CSCs have been identified in prostate tissue by the use of several markers or techniques. Although research on stem cells has been limited by the lack of suitable in vitro systems, recent studies show that not only primary cells but also several established cell lines may exhibit stem cell properties. This review discusses various in vitro culture systems to propagate normal prostate stem cells and prostate CSCs together with molecular markers. These in vitro cell culture models should be useful for elucidating the differentiation of prostatic epithelium and the biological features of prostate cancer.     

Tissue print micropeel: A new technique for mapping tumor invasion in prostate cancer

Because of widely adopted screening programs for early detection of prostate cancers, many patients who undergo radical prostatectomy have tumors that are not grossly evident, and the extent and distribution of the cancer in the gland can only be determined by a microscopic examination of the surgical specimen. Historically, one of the most important predictors of the quality of cancer control following surgical resection of a solid tumor is the absence of cancer at the surgical margins. Although the clinical significance of cancer at the margins of a radical prostatectomy specimen has been a source of controversy in recent years, surgical pathology assessment of radical prostatectomy margins remains an important part of prostate cancer clinical care. However, a comprehensive histopathologic review of every radical prostatectomy specimen is beyond the resources of most hospitals. Tissue print micropeel technologies, combined with appropriate markers, provide a new strategy that combines a relatively simple technique for sampling specimen margins with a method for obtaining molecular information about the cancer that can add to the macroscopic and microscopic anatomical findings. This new tissue printing approach for incorporating molecular markers into the assessment of radical prostatectomy margins is reviewed in this article.     

The clinical role of prostate-specific membrane antigen (PSMA)

Prostate cancer remains the most common cancer type in men in the United States. Efforts are increasing to evaluate and to discover diagnostic and therapeutic markers for prostate cancer patients. One of these, prostate-specific membrane antigen (PSMA), is a transmembrane protein highly expressed in all types of prostatic tissue, especially cancer. The radio-immunoconjugate form of the anti-PSMA monoclonal antibody (mAb) 7E11, known as the ProstaScint scan, is currently being used to diagnose prostate cancer metastasis and recurrence. Early promising results from various Phase I and II trials have utilized PSMA as a therapeutic target. Recently, PSMA expression in endothelial cells of tumor-associated neovasculature has been described. PSMA's possible role in malignant angiogenesis newly expands the realm of its possible beneficial uses, especially as new anti-PSMA mAbs continue to be developed and refined.