前列腺癌生物标志物的研究进展

前列腺癌(PCa)是一种发生于前列腺组织中的恶性肿瘤,是前列腺腺泡细胞异常无序生长的结果.PCa发病率具有明显的地理和种族差异,在欧美等发达国家和地区,是男性最常见的恶性肿瘤,病死率居各种癌症第2位[1];在亚洲,其发病率低于西方国家,但近年来随着人口老龄化及生活条件的改善,发病率呈迅速上升趋势[2];在我国,PCa在男性泌尿、生殖系统恶性肿瘤中发病率已跃居第3位,患者主要是老年人,严重影响着我国老年男性的晚年生活质量[3,4].PCa的生存率有赖于早期的诊断和治疗,生物标志物往往能先于其他手段如直肠指检(DRE)、超声等检出癌症,故寻找有效的生物标志物一直是研究的热点.现就PCa生物标志物研究进展作一综述.     

多肿瘤标志物蛋白芯片诊断前列腺癌

目的:探讨多肿瘤标志物蛋白质芯片检测系统在筛查高危人群前列腺癌发生中的作用.方法:采用多肿瘤标志物蛋白质芯片检测系统检测泌尿外科189例前列腺疾病患者血清中12种肿瘤标志物CA19-9、CA242、CEA、AFP、NSE、Ferritin、β-HCG、fPSA、tPSA、CA125、CA15-3、HGH的含量.结果:189例前列腺疾病患者血清中,fPSA和tPSA升高超过正常者分别为15.3%(29/189)和39.7%(75/189),病理诊断前列腺癌共13例,fPSA和tPSA联合诊断前列腺癌的敏感性和特异性分别为100%(13/13)和64.8%(114/176).结论:多肿瘤标志物蛋白质芯片检测系统是进行快速和规模性筛查前列腺癌的可行和有效手段.     

AGR2蛋白在前列腺癌组织中的表达及意义

目的探讨AGR2蛋白在前列腺癌组织中的表达及意义。方法利用Real-time RT-PCR、RT-PCR和免疫组织化学方法检测AGR2在不同的细胞系以及前列腺癌组织中的表达。结果 AGR2的表达与前列腺癌的进展呈正相关。结论 AGR2蛋白可作为前列腺癌进展诊断的候选分子标志物。     

前列腺干细胞抗原与前列腺癌

人们对前列腺癌早期诊断的标志物及理想的治疗靶点的探寻从未停止过脚步。迄今为止,一批潜在的将用于诊治前列腺癌的候选蛋白逐步浮现。其中一个新发现的重要的生物标志物是前列腺干细胞抗原（PSCA）。PSCA是一种糖化磷脂酰肌醇（GPI）锚定的细胞膜表面糖蛋白,属于Thy-1/Ly-6家族成员之一,在人前列腺癌细胞中高表达,在正常前列腺组织中表达有限。正是这样的组织特异性,使其成为前列腺癌诊断和预后判断的一个潜在的标志物和颇具吸引力的免疫治疗的候选靶点。研究显示,PSCA表达的增加与前列腺癌Gleason评分、肿瘤分期和骨转移均具有相关性。PSCA作为前列腺癌特异的膜抗原,具有严格的表达模式,现其已被作为免疫治疗的靶点而进行深入研究,如利用单克隆抗体、结合细胞毒的抗体、遗传工程T细胞、PSCA疫苗和负载肽段的树突状细胞（DC）等手段进行免疫治疗。本文主要对PSCA在前列腺癌诊断、预后判断、治疗等方面的研究加以综述,同时简要介绍一些PSCA在其他肿瘤中与在前列腺癌中表达情况不同的研究报告。     

组学方法筛选结核病生物标志物的应用进展

结核病目前仍然是世界范围内最严重的传染病之一。现有结核病诊断方法不能有效区分潜伏感染和活动性结核病例,延误后续的干预治疗。生物标志物含量在结核病潜伏感染、活动性结核等不同阶段存在差异,有望在感染早期做出预警。因此,筛选新的潜在结核病生物标志物,建立有效、快速、灵敏的诊断方法,有助于更早发现并及时采取结核病防治干预措施。随着基因组、转录组、蛋白组、代谢组等组学方法的发展,高通量筛选结核病生物标志物成为可能。交叉组学的应用还能够进一步提高生物标志物筛选的可靠性。本文就组学方法筛选结核病生物标志物的应用进行介绍,以期为新型结核病诊断方法研发提供线索。     

呼出气体冷凝物的蛋白质组学研究用于肺癌早期诊断的探讨

蛋白质组学研究的新方法、新技术的出现使其在肿瘤的研究中展现出广阔的应用前景。呼出气体冷凝物是一种尚处于研究阶段的无创、简易的新型检测肺癌的方法,包含了一系列来源于下呼吸道的生物标志物,如蛋白质。从这一视角分析以呼出气体冷凝物为样本、蛋白质组学技术为研究手段,来检测肺癌肿瘤标志物的潜力及面临的局限,论述其用于肺癌早期诊断...     

心肌损伤标志物即时检测技术的应用进展

快速检测心肌损伤标志物可以为急性心肌梗死诊断提供重要依据。该文主要对纸基类检测、生物传感器、微流控芯片技术和可穿戴设备等即时检测技术在检测心肌损伤标志物中的应用作一介绍。     

急性心肌梗死交感应激相关生物标志物研究进展

急性心肌梗死(AMI)作为常见的心血管疾病，发病率和死亡率呈逐年上升态势，严重危害着人们的生命健康。传统心血管生物标志物的临床应用，极大促进了AMI的诊断、风险分层、治疗和预后。寻找新型生物标志物并将其应用于AMI的临床实践仍是目前研究的重要方向。交感应激在AMI中发挥着重要作用。现就近年来有关交感应激相关生物标志物与AMI关系的研究进行总结，以探讨此类标志物用于AMI诊断、风险分层及预后的可行性。     

前列腺特异性抗原及骨标志物检测对前列腺癌骨转移患者诊断的意义

目的 探讨前列腺特异性抗原(PSA)、骨形成标志物碱性磷酸酶(ALP)与骨吸收标志物抗酒石酸酸性磷酸酶5b(TRACP5b)、Ⅰ型胶原吡啶交联终肽(ICTP)在前列腺癌骨转移诊断的意义. 方法 通过测定57例老年前列腺癌患者(年龄61～90岁)PSA、TRACP5b、ALP、ICTP血清浓度,分成骨转移(27例)与非骨转移(30例)两组,以转移灶在5个及以上者划分为进展性(18例)和局限性骨转移(39例).采用受试者工作特征曲线( ROC)评估各标志物诊断前列腺癌骨转移的价值.结果 PSA、TRACP5b、ALP、ICTP血清浓度在前列腺癌骨转移组均高于非骨转移组(P＜0.05);与局限性骨转移组比较,PSA、TRACP5b、ALP、ICTP、Gleason评分在进展性骨转移组中均有明显升高(P＜0.05);PSA、TRACP5b、ALP、ICTP诊断前列腺癌骨转移的曲线下面积(AUC)分别为0.796、0.657、0.762、0.743,最高诊断价值的是PSA,ALP、ICTP与之相当,TRACP5b次之,其敏感性分别为66.7％、59.3％、37.0％、59.3％,特异性则为90.0％、96.7％、80.0％、76.7％;PSA、ALP、ICTP与Gleason评分是预测前列腺癌骨转移的独立性因素,总符合率为84.2％. 结论 PSA、TRACP5b、ALP、ICTP诊断前列腺癌骨转移的价值相当,联合检测并动态观察可能有利于前列腺癌骨转移的早期诊断.     

Molecular prostate cancer pathology: current issues and achievements

Recent developments in the field of molecular techniques have provided new tools that have led to the discovery of many new promising biomarkers for prostate cancer. These biomarkers may be instrumental in the development of new tests that will have a high specificity for the diagnosis and prognosis of prostate cancer. A biomarker is defined as a molecular test that provides additional information to currently available clinical and pathological tests. Biomarkers should be reproducible (both within and between institutes) and have an impact on clinical management. For diagnostic purposes it is important that potential biomarkers are tested in terms of tissue specificity and their discrimination potential between prostate cancer, normal prostate and benign prostatic hyperplasia. The results of (multiple) biomarker-based assays may enhance the specificity of cancer detection. There is an urgent need for molecular prognostic biomarkers for predicting the biological behavior and outcome of cancer.     

Molecular Diagnostics in Prostate Cancer

Since there are no effective therapeutic options for advanced prostate cancer, early detection of this tumour is pivotal and can increase the curative success rate. Although the routine use of serum PSA testing has undoubtedly increased prostate cancer detection, one of its main drawbacks has been the lack of specificity that results in a high negative biopsy rate. Since prostate cancer is a heterogeneous disease, it has become clear that a defined set of markers will provide significantly more diagnostic information than any one biomarker. The list of potential prostate cancer biomarkers will continue to grow. Only when research groups use the proposed guidelines for biomarker development, then systematic evaluation and clinical investigation of these biomarkers will gain more insight into their true diagnostic potential.     

Biomarkers for the detection and prognosis of prostate cancer

Recent studies have cast doubt on the reliability of serum total prostate-specific antigen as a biomarker for the detection and prognosis of prostate cancer. Biomarkers that can identify those men at risk for clinically significant prostate cancer are desperately needed. The search for biomarkers that may improve the detection of biologically consequential prostate cancer is one of the most active areas under current investigation. In this review, we highlight some of these ongoing efforts. Proper validation of newly discovered biomarkers is of paramount importance.     

肝细胞癌生物标志物的研究进展:对于临床诊断及预后的意义

肝细胞癌(HCC)是2020年癌症死亡的第三大原因,也是全球第六大常见癌症。大多数肝癌患者在就诊时已发展为晚期癌症,尽管HCC发病率很高,但对于晚期患者的治疗方案并不多,所以提高HCC患者的早期发现率非常必要。本文总结HCC中已发现的生物标志物,希望能够为肝癌的早期诊断和预后判断提供新的视角。     

Biomarker research in prostate cancer--towards utility, not futility

The identification of an appropriate clinical question is critical for any biomarker project. Despite rapid advances in technology, few biomarkers have been forthcoming for prostate cancer. This could be because the clinical questions under investigation have not actually originated from clinical practice. These clinical questions are difficult to identify in the complex and heterogeneous pathogenesis of prostate cancer. In this Review, we have developed a prostate cancer 'roadmap' to identify the aspects of prostate cancer that may be amenable to biomarker discovery and serve as a guide for future projects in prostate cancer biomarker research.     

Epithelial-to-mesenchymal transition in prostate cancer: paradigm or puzzle?

The lethal consequences of prostate cancer are related to its metastasis to other organ sites. Epithelial-to-mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm to explain invasive and metastatic behavior during cancer progression. EMT is a normal physiologic process by which cells of epithelial origin convert into cells bearing mesenchymal characteristics. It has been proposed that EMT is co-opted by cancer cells during their metastatic dissemination from a primary organ to secondary sites, but the extent to which this recapitulates physiologic EMT remains uncertain. However, there is ample evidence that EMT-like states occur in, and may contribute to, prostate cancer progression and metastasis, and so has become a very active area of research. Here we review this evidence and explore recent studies that have aimed to better define the role and mechanisms of EMT in prostate cancer. While definitive evidence of something akin to physiologic EMT is still lacking in human prostate cancer, this area of research has nonetheless provided new avenues of investigation into the longstanding puzzles of metastasis, therapeutic resistance, and prognostic biomarkers.     

Advances in epigenetic biomarker research in colorectal cancer

Colorectal cancer(CRC)causes approximately 600000deaths annually and is the third leading cause of cancer mortality worldwide.Despite significant advancements in treatment options,CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making.Since there exists a need to find new biomarkers to improve diagnosis of CRC,the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice.Epigenetic alterations are thought to hold great promise as tumor biomarkers.In this review,we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers,including DNA methylation,microRNA expression and histone modification,in cancer tissue,stool,plasma,serum,cell lines and xenografts.These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening,early diagnosis,prognosis,therapy choice and recurrence surveillance for CRC patients.However,these studies have typically been small in size,and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use.     

Biomarkers for lung cancer: clinical uses

PURPOSE OF REVIEW: Biomarkers for lung cancer may be used for risk stratification, early detection, treatment selection, prognostication and monitoring for recurrence. All these areas of clinical management would benefit from sensitive and specific, noninvasive, cost-effective biomarkers. RECENT FINDINGS: Significant progress has been made in understanding the steps involved in lung carcinogenesis and in the development of novel technologies for biomarker discovery. Over the last 3 years research into prospective lung cancer biomarkers has proliferated, especially in the areas of early detection and prognostication. The most active areas of research have been in promoter methylation, proteomics and genomics. Many investigators are adopting panels of serum biomarkers in an attempt to increase sensitivity. The development of targeted lung cancer therapy has engendered interest in markers to identify the optimal candidates for these therapies. SUMMARY: Much progress has been made in the last 3 years in the identification and validation of new biomarkers for the early diagnosis of lung cancer. The biomarkers require additional studies before they can be used clinically. Markers to identify lung cancer patients who may benefit from targeted therapy have been developed more rapidly and may be used now in some clinical situations.     

Proteomic patterns: their potential for disease diagnosis

Alterations in proteins abundance, structure, or function, act as useful indicators of pathological abnormalities prior to development of clinical symptoms and as such are often useful diagnostic and prognostic biomarkers. The underlying mechanism of diseases such as cancer are, however, quite complicated in that often multiple dysregulated proteins are involved. It is for this reason that recent hypotheses suggest that detection of panels of biomarkers may provide higher sensitivities and specificities for disease diagnosis than is afforded with single markers. Recently, a novel approach based on the analysis of protein patterns has emerged that may provide a more effective means to diagnose diseases, such as ovarian and prostate cancer. The method is based on the use of surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry (TOF-MS) to detect differentially captured proteins from clinical samples, such as serum and plasma. This analysis results in the detection of “proteomic” patterns that have been shown in recent investigations to distinguish diseased and unaffected subjects to varying degrees. This review will discuss the basics of SELDI protein chip technology and highlight its recent applications in disease biomarker discovery with emphasis on cancer diagnosis.     

The emerging roles of DNA methylation in the clinical management of prostate cancer

Aberrant DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than 20 years. The role of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution to the early stages of tumour development to the advanced stages of androgen independence. The most significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain family 1A (RASSF1A) and retinoic acid receptor beta2 (RARbeta2) that become inactivated through promoter hypermethylation during the course of disease initiation and progression. This has provided the basis for translational research into methylation biomarkers for early detection and prognosis of prostate cancer. Investigations into the causes of these methylation events have yielded little definitive data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of prostate cancer.