蛋白质组学在肿瘤标志物研究中的进展

随着人类基因组计划的完成，功能基因组学研究日益深入，蛋白质组学就成为人们研究的热点。广义上讲，蛋白质组（proteome）是指“一个细胞或一个组织基因组在一定条件下所表达的全部蛋白质”。蛋白质组学（proteomics）是指以蛋白质组为研究对象，从整体的角度，分析细胞内动态变化的蛋白质组成与活动规律。     

蛋白质组学在肿瘤标志物研究中的进展

随着人类基因组计划的完成,功能基因组学研究日益深入,蛋白质组学就成为人们研究的热点。广义上讲,蛋白质组(proteome)是指“一个细胞或一个组织基因组在一定条件下所表达的全部蛋白质”。蛋白质组学(proteomics)是指以蛋白质组为研究对象,从整体的角度,分析细胞内动态变化的蛋白质组成与活动规律[1]。肿瘤发生过程中,细胞恶变前后的表达蛋白质组发生了变化。应用蛋白质组学研究技术比较肿瘤发生过程中蛋白质的变化,可以发现肿瘤相关的特异蛋白质,不仅为肿瘤诊断提供分子标志,也可能为肿瘤的治疗和药物开发提供靶标。本文就比较蛋白质组学技…     

蛋白质组学在肝癌研究中的进展

蛋白质组学是继基因组学后出现的一门新兴学科，其技术平台由高通量的蛋白质分离技术、鉴定技术和生物信息学组成，近年来蛋白质组学发展十分迅速，现就蛋白组学的基本技术流程及蛋白组学在肝癌研究中的新进展进行综述。     

蛋白质组学及其在肿瘤标志物研究中的应用

2001年2月人类基因组图谱基本绘制完成,但对基因调节与功能等问题仍未能解读,被赋予研究基因表达调节及其产物功能任务的"后基因组学"即应运而生[1].     

蛋白质组学在结直肠癌生物标志物研究中的应用

蛋白质组学是以蛋白质组为研究对象的一门崭新的生命科学,其技术主要包括样品的制备技术、双向凝胶电泳、差异凝胶电泳、多维蛋白质鉴定技术和表面增强激光解析电离飞行时间质谱等。结直肠癌是人类最常见的恶性肿瘤之一,近几年蛋白质组学在结直肠癌生物标志物的研究中取得了很大进展。本文对此作一综述。     

蛋白质组学在原发性肝癌中的研究进展

近年来,蛋白质组学作为一门新兴学科,越来越受到研究者的普遍关注。随着蛋白质组学技术日趋成熟,这种探索蛋白质结构和功能的科研方法深入到了各个疾病领域。原发性肝癌是一种以高死亡率为特征的常见癌症,运用蛋白质组学技术,可以充分了解疾病的发生、发展机制,并在寻找诊断标记物和药物靶向治疗方面产生价值。如今,世界各地的研究人员正在运用不同的蛋白质组学技术对原发性肝癌进行深入研究,并取得了相应进展。     

蛋白质组学及其研究技术在肺癌分子生物标志物研究中的应用

肺癌是全球发病率和死亡率较高的恶性肿瘤。细胞从正常状态转变为肿瘤的过程中，细胞内蛋白质表达谱必然会发生一系列变化，肿瘤分子标记物就是细胞在非正常状态下产生的分子．以高通量结合生物信息学为特点的蛋白质组学分析技术可以从细胞整体水平上检测到这种变化近年来，为了降低肺癌的死亡率并提高其治疗效果，研究人员利用这一新的手段如利用激光捕获显微切割技术和双相凝胶电泳结合基质辅助激光解析电离飞行时间质谱（MALDI-TOF MS）和表面增强激光解析电离色行时间质谱（SELDI—TOF MS）寻找有效的肺癌标记物。本文对蛋白质组学技术在肺癌生物标志物研究中的应用作了综述。     

蛋白质组学研究在确定新的肿瘤标志物中的意义

随着蛋白质组学技术、高通量技术及生物信息学技术的发展，越来越多的肿瘤标志物被发现，并将逐步应用于临床，这些进展必将为肿瘤的早期检测和风险评价提供可靠的依据。现综述蛋白质组学研究策略在肿瘤标志物的筛选和鉴定中的应用。     

蛋白质组学在实体瘤肿瘤标志物研究中的应用

在后基因组时代,生物学的中心任务是认识基因组的功能。由于基因功能主要是通过其表达蛋白质来实现的,要了解基因的全部信息,必须深入研究不同基因编码的蛋白质,因此蛋白质组学在生命科学研究中已具有重要的地位。肿瘤细胞或组织蛋白质样本通常经过双向电泳等技术可以按不同大小、等电点或类型得以分离(profiling),然后通过质谱技术和蛋白质数据库比较,进一步将特殊的感兴趣的蛋白质鉴定出来。肿瘤蛋白质组学是整个蛋白质组学研究中的一项重要内容,通过蛋白质组分析技术将能够从细胞整体水平上认识在肿瘤的发生、发展过程中蛋白表达谱的变化,为寻找特异的肿瘤标志物这一研究领域带来了新的希望。近几年来,使用蛋白质组学和激光捕获显微切割技术(laser capture microdissection,LCM)已在多种肿瘤中发现了许多有研究前景的肿瘤标志物侯选蛋白,尽管目前被肯定的肿瘤特异性标志物尚为数不多,但和以往相比已经有了十分显著的进步,本文对此做了简要综述。     

差异蛋白质组学及其在筛选肝癌血清标志物的研究进展

探寻特异性强和灵敏度高的肝癌早期诊断标记物,进一步提高肝癌早期诊断水平,是目前肝癌综合防治研究的重点之一.随着人类基因组计划的初步完成以及蛋白质组学技术的成熟发展,肿瘤标志物研究领域的重心从结构基因组学向功能蛋白质组学转移.差异(比较)蛋白质组学研究在疾病的早期诊断、病程及疗效监测、环境因素影响分析等方面有广泛的研究价值.本文就其应用于寻找肝癌血清标志物的研究进展做一综述.     

Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

Objective： To discover new proteomic biomarkers of hepatocellular carcinoma. Methods： Surface enhanced laser desorption/ionization time-of-flight （SELDI-TOF） mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results： Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion： Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.     

Comparative analysis of the liver and plasma proteomes as a novel and powerful strategy for hepatocellular carcinoma biomarker discovery

The extraordinary developments made in the past decade in proteomic technologies, in particular in mass spectrometry, have enabled investigators to consider designing studies to search for diagnostic and therapeutic biomarkers by scanning complex proteome samples. We developed a method based on extensive fractionation of intact proteins, to comprehensively and quantitatively profile the liver and plasma proteomes in health and disease. We have applied this method to samples collected from patients with early hepatocellular carcinoma (HCC) and from patients with liver cirrhosis as well as to samples collected from three mouse models of HCC. This method allowed for the identification of proteins that differ in expression levels in liver tissue or in plasma with disease progression from liver fibrosis, cirrhosis or steatohepatitis to HCC. The comparative analysis of the liver and plasma proteomes generated from human and mouse specimens, constitutes a novel and powerful strategy for HCC biomarker discovery.     

肝细胞癌蛋白质组学研究进展

近年来的肝细胞癌(HCC)蛋白质组学研究表明,在不同生物学行为的HCC细胞株和HCC患者肿瘤组织及癌旁组织中发现并鉴定了许多特定的差异蛋白,在不同背景下的HCC患者血清中筛选出特定的差异蛋白和自身抗体,以及在HCC动物模型中发现了新的药物靶点。这些有潜在价值的用于HCC诊断和预后的分子标记物和治疗的药物靶点,能够给HCC的诊断和治疗带来新的动力。     

Identifying serological biomarkers of hepatocellular carcinoma using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy

Lack of sensitive and specific biomarkers is a major reason for the high rate of hepatocellular carcinoma (HCC) related mortality. The aim of this study was to use surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS) technology to identify potential protein patterns specific for HCC. Eighty-one patients with hepatitis B-related HCC and 80 healthy controls were randomly divided into a training set (48 HCC, 47 controls) and a testing set (33 HCC, 33 controls). Serum proteomic profiles were measured using SELDI-TOF-MS. A classification tree was established by Biomarker Pattern Software. Candidate biomarkers were separated by HPLC and identified by MALDI-MS/MS and database searching. Forty-eight HCC cases, 54 liver cirrhosis cases and 42 healthy people were clinically validated using candidate biomarkers by SELDI-Immunoassay. Two up-regulated protein peaks were automatically chosen as a classification tree in the training set. These biomarkers were identified as thrombin light chain and growth related oncogene-α (GRO-α). The sensitivity and specificity of this classification tree were 89.6%. The multivariate model using the two biomarkers and AFP resulted in a sensitivity of 91.7% and specificity of 92.7%, which was significantly better than that of alpha-fetoprotein alone. We conclude that thrombin light chain and GRO-α are potential biomarkers of HCC.     

蛋白质组学在肿瘤生物标记筛选中的应用

蛋白质组学的快速发展为肿瘤生物标记的研究提供了科学的理论依据,在乳腺癌、结直肠癌、鼻咽癌及肝细胞癌等癌症的早期诊断方面发挥了重要作用,一些新的肿瘤生物标记相继被发现,如细胞质泛素、钙结合蛋白、血浆铜蓝蛋白和胆绿素还原酶等.了解这些标记物的表达机制,对癌症的诊断和治疗有重要意义.     

蛋白质组学在寻找肝癌生物标记物中的研究进展

蛋白质组学技术的快速发展和广泛应用,为寻找特异性肝癌标记物提供了值得探索的有效手段。近年来在肝癌血清、组织和细胞系中,许多有潜在价值的新标记物相继被发现。     

Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery

Esophageal squamous cell carcinoma (ESCC) is among the top ten most frequent malignancies worldwide. In this study, our objective was to identify potential biomarkers for ESCC through a quantitative proteomic approach using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from ten patients. LC-MS/MS analysis of strong cation exchange chromatography fractions was carried out on an Accurate Mass QTOF mass spectrometer, which led to the identification of 687 proteins. In all, 257 proteins were identified as differentially expressed in ESCC as compared to normal. We found several previously known protein biomarkers to be upregulated in ESCC including thrombospondin 1 (THBS1), periostin 1 (POSTN) and heat shock 70 kDa protein 9 (HSPA9) confirming the validity of our approach. In addition, several novel proteins that had not been reported previously were identified in our screen. These novel biomarker candidates included prosaposin (PSAP), plectin 1 (PLEC1) and protein disulfide isomerase A 4 (PDIA4) that were further validated to be overexpressed by immunohistochemical labeling using tissue microarrays. The success of our study shows that this mass spectrometric strategy can be applied to cancers in general to develop a panel of candidate biomarkers, which can then be validated by other techniques.     

Mutation and clinical significance of c-fms oncogene in hepatocellular carcinoma

c-fms oncogene locates at 5q33.3 of human chromo-some, it encodes for colony-stimulating factor 1 receptor (CSF-1R), CSF-1R has the activity of tyrosine kinase. With the method of successive slicing, we have found that c-fms/CSF-1R was highly expressed in HCC (hepatocellular carcinoma) tissue.[1] PCR-SSCP (poly-merase chain reaction-single-strand conformation poly-morphism) technique was used to further clarify the mechanism of its abnormal activation, the character of c-fms in hepatoc…     

High KIF18A expression correlates with unfavorable prognosis in primary hepatocellular carcinoma

This study aimed to investigate KIF18A expression in hepatocellular carcinoma (HCC) and to determine the possibility of KIF18A expression being a biomarker in HCC diagnosis or being an independent predictor of disease-free survival (DFS) and overall survival (OS) in HCC patients underwent surgical resection. KIF18AmRNA was detected in 216 cases of HCC tissues by quantitative real-time PCR (qRT-PCR) and in 20 cases of HCC tissues by semi-quantitative RT-PCR. KIF18A protein was determined in 32 cases of HCC tissues by immunohistochemistry (IHC). The survival probability was analyzed by Kaplan-Meier method, and survival curves between groups were obtained by using the log-rank test. Independent predictors associated with DFS were analyzed with Stepwise Cox proportional hazard models. High KIF18A mRNA level was detected in 154 out of 216 (71.3%) cases of HCC. The positive rate of KIF18A expression was significantly higher in liver cancer tissues than that in adjacent normal liver tissues (ANLT) from HCC patients [65.6% (21 of 32) vs. 25.0% (8 of 32), P=0.001]. The KIF18A expression level had positive relevance to the alpha-fetoprotein (AFP) (≥200 ng/ml), tumor size (≥5cm), clinical tumor-node-metastasis (TNM) stage and portal vein tumor thrombus (PVTT) in HCC (all P <0.05). A survival analysis indicated that HCC patients with higher KIF18A expression had a significantly shorter DFS and OS after resection. A multivariate analysis suggested that KIF18A upregualtion was an independent factor for DFS [hazard risk (HR)=1.602; 95% confidence interval (CI), 1.029-2.579; P=0.031] and OS (HR=1.682; 95% CI, 1.089-2.600; P=0.019). KIF18A might be a biomarker for HCC diagnosis and an independent predictor of DFS and OS after surgical resection.     

肝细胞癌HLA—DR抗原的研究及意义

目的：探讨人白细胞DR抗原(HLA-DR)在人原发性肝细胞癌(简称肝癌)的表达情况及其意义。方法：分别采用免疫组化ABC法和流式细胞仪检测了HLA-DR在46例人肝癌组织和4种培养的人肝癌细胞系(SMMC-7721、HCC-9204、BEL-7402和HHCC)的表达情况。结果：39.1％(18／46例)的肝癌组织癌细胞可表达HLA-DR,而在癌旁非肿瘤细胞为阴性。4种肝癌细胞系都基本上不表达HLA-DR。结论：肝癌组织可在一定程度上表达HLA-DR,但是培养的肝癌细胞系基本上不表达。HLA—DR与肝癌发生、发展的关系及其在抗肝癌免疫应答中的作用有待进一步研究。