蛋白质组学在肝癌及其相关疾病研究中的应用

肝癌是世界上死亡率最高的恶性肿瘤之一,病毒性肝炎、肝纤维化、肝硬化等都是肝癌主要的致病原.随着后基因组时代的到来,运用蛋白质组学技术对肿瘤及其相关疾病的研究已经成为人们关注的焦点.本文着重就蛋白质组学在肝癌及其相关疾病研究中的应用作一综述.     

蛋白质组学在肝癌研究中的应用

肝癌的发病机制至今仍不明了,且缺乏有效的早期诊断方法和治疗靶点.以往对肝癌的研究多数集中于单个或少数几个基因或蛋白质,随着蛋白质组学技术和方法的迅速发展,从整体上探讨肝癌这类多基因、多蛋白参与的疾病生化过程成为可能.现综述近年来蛋白质组学在肝癌研究中的应用进展     

蛋白质组学在肝癌研究中的应用

肝癌的发病机制至今仍不明了,且缺乏有效的早期诊断方法和治疗靶点.以往对肝癌的研究多数集中于单个或少数几个基因或蛋白质,随着蛋白质组学技术和方法的迅速发展,从整体上探讨肝癌这类多基因、多蛋白参与的疾病生化过程成为可能.现综述近年来蛋白质组学在肝癌研究中的应用进展     

原发性肝癌蛋白质组学研究进展

继人类基因组研究之后,蛋白质组学成为当前生物医学研究的热点。蛋白质组学的不断发展,使我们可以深入理解基因级研究不能明确的细胞和分子机制,促进了肝癌在分子机制上更全面的研究,为了解原发性肝癌的发病机制、早期诊断和预防及治疗提供重要的理论基础。     

蛋白质组学在肝癌标志物研究中的应用

近年来蛋白质组学被广泛地应用于各种疾病研究，已由原来单一的比较蛋白质组学研究拓展到如今涉及功能蛋白质、蛋白质间相互作用等多方面的研究；有关蛋白质组学在肝癌标志物研究中的应用对于肝癌的诊断有重要的意义。     

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。     

蛋白质组技术在原发性肝癌研究中的应用

原发性肝癌是常见、高发的恶性肿瘤之一。由于肝癌是多因素、多阶段发展的癌症，早期症状隐匿，常规治疗后易复发转移，预后凶险等特点，已成为我国恶性肿瘤的第2位杀手。目前在常规手术及药物治疗手段无突破性进展情况下，基于基因及蛋白质组水平的研究已经成为原发性肝癌研究的突破点。基因是遗传信息的携带者，蛋白质则是生命活动的执行者。随着人类基因组计划的完成，人们将目光转移到后基因组学研究上来，所以肝癌的蛋白质组变化逐渐成为研究的重点。蛋白质组学技术的运用及发展，使得数以千计的基因和蛋白质的分析成为可能，为探索早期发现、分类、评价预后的肿瘤标志物及选择更加有效的、准确的肿瘤治疗靶点提供了可靠的保证。本文就蛋白质组技术在原发性肝癌研究中的应用做一综述。     

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.     

蛋白质组学技术及其在肝病研究中的应用

目的 蛋白质组学是继基因组学之后出现的一门新兴学科,已成为当前生物医学领域研究的热点,在肝脏疾病研究中已广泛应用并取得较大进展,本文综述蛋白质组学技术及其在肝病研究中的应用概况.     

蛋白质组学研究进展及在泌尿系肿瘤研究中的应用

  蛋白质组学是一门以蛋白质组为研究对象、以全面的蛋白质性质研究为基础，在蛋白质水平对疾病机制进行探索的科学。蛋白质芯片SELDI- TOF-MS技术是蛋白质组学研究的全新技术平台，具有广阔的应用前景。作者就蛋白质组学相关技术原理、研究进展及在泌尿系肿瘤研究中的应用作了阐述。     

Application of Proteomics to the Study of Hepatocellular Carcinoma and Some Related Diseases

Hepatocellular carcinoma is a malignant tumor causing one of the highest death rates in the world. Viral hepatitis, hepatic fibrosis and hepatocirrhosis etc. Are some of the most important causes of hepatocellular carcinoma. With the advent of the post-genomic age, studying carcinoma and some related diseases using the developing technology of proteomics has become a major focus of researchers. This article is a review of the application of proteomics to study hepatocellular carcinoma and some related diseases.     

Research Progress in Applying Proteomics Technology to Explore Early Diagnosis Biomarkers of Breast Cancer,Lung Cancer and Ovarian Cancer

According to the China tumor registry 2013 annual report , breast cancer, lung cancer, and ovarian cancer arethree common cancers in China nowadays, with high mortality due to the absence of early diagnosis technology.However, proteomics has been widespreadly implanted into every field of life science and medicine as an importantpart of post-genomics era research. The development of theory and technology in proteomics has provided newideas and research fields for cancer research. Proteomics can be used not only for elucidating the mechanismsof carcinogenesis focussing on whole proteins of the tissue or cell, but also seeking the biomarkers for diagnosisand therapy of cancer. In this review, we introduce proteomics principles, covering current technology used inexploring early diagnosis biomarkers of breast cancer, lung cancer and ovarian cancer     

Implementation of Proteomics for Cancer Research: Past,Present, and Future

Cancer is the leading cause of the death, accounts for about 13% of all annual deaths worldwide. Manydifferent fields of science are collaborating together studying cancer to improve our knowledge of this lethaldisease, and find better solutions for diagnosis and treatment. Proteomics is one of the most recent and rapidlygrowing areas in molecular biology that helps understanding cancer from an omics data analysis point of view.The human proteome project was officially initiated in 2008. Proteomics enables the scientists to interrogate avariety of biospecimens for their protein contents and measure the concentrations of these proteins. Currentnecessary equipment and technologies for cancer proteomics are mass spectrometry, protein microarrays,nanotechnology and bioinformatics. In this paper, we provide a brief review on proteomics and its application incancer research. After a brief introduction including its definition, we summarize the history of major previouswork conducted by researchers, followed by an overview on the role of proteomics in cancer studies. We alsoprovide a list of different utilities in cancer proteomics and investigate their advantages and shortcomings fromtheoretical and practical angles. Finally, we explore some of the main challenges and conclude the paper withfuture directions in this field.     

蛋白质组学研究技术及其在烷化剂引起的细胞应答反应研究中的应用

蛋白质组学是后基因组时代的一个新兴领域,其理论和技术的发展为化学致癌物致突变的分子机制的研究提供了新的思维方式.本文回顾了蛋白质组学的研究技术,包括双向凝胶电泳、质谱和生物信息学近年的主要进展,并介绍了本实验室利用蛋白质组学的技术,研究低浓度烷化剂引起的细胞应答反应所取得的初步结果.     

Targeted Proteins Reveal Cathepsin D as a Novel Biomarker in Differentiating Hepatocellular Carcinoma from Cirrhosis and Other Liver Cancers

Objective: Hepatocellular carcinoma (HCC) represents a global health concern, particularly in Southeast Asia where hepatitis B virus (HBV) infection is common. In this study, we applied tissue-based proteomics to identify novel serological proteins for HCC and validated their performance in serum specimens. Methods: In a discovery set, liver tissue specimens of HBV-related HCC, intrahepatic cholangiocarcinoma (iCCA) and colorectal cancer with liver metastasis (CRLM) were analyzed using mass spectrometry (LTQ-Orbitrap-XL). A subset of proteins that showed highly expressed in HCC were then confirmed by Western blotting. Additionally, clinical significance of selected candidate proteins was tested in serum samples of 80 patients with HBV-related HCC, 50 patients with HBV-related liver cirrhosis and 30 healthy controls. Results: Based on LTQ-Orbitrap-XL mass spectrometer, various differentially expressed proteins (DEPs) between tumor and adjacent non-tumor tissues were identified. These included 77 DEPs for HCC, 77 DEPs for iCCA and 55 DEPs for CRLM. Among selected candidate proteins, annexin A2 and cathepsin D were confirmed to be overexpressed in HCC tissue by Western blot analysis. In a validate cohort, serum cathepsin D level, but not annexin A2, was significantly higher in HCC compared with the non-HCC groups. Serum cathepsin D level was also positively correlated with tumor size and tumor stage. Additionally, the combined assay of serum cathepsin D and alpha-fetoprotein had a high sensitivity in detecting early HCC (83%) and intermediate/advanced HCC (96%). Moreover, patients with low serum cathepsin D (<305 ng/mL) displayed significantly better overall survival than those whose serum levels were high (≥305 ng/mL). Conclusions: Proteomics and subsequent validation revealed cathepsin D as a novel biomarker for HCC. Apart from its diagnostic role, serum cathepsin D might also serve as a prognostic biomarker of HCC. Additional large-scale studies are needed to verify our findings.     

蛋白质组学在肿瘤防治研究中的应用

随着人类基因组测序计划 (humangenomesequenceproject)的完成 ,产生了蛋白质组学 (proteomics) --研究细胞内全部蛋白质的组成及动态变化的一门新兴学科。恶性肿瘤是一种多种基因和蛋白质参与的复杂疾病。综述了在肿瘤防治中蛋白质组学的主要策略和技术 ,及其在肿瘤标志物的筛选和鉴定、肿瘤分类、预后、治疗效果的评价及肿瘤发生机制等方面的研究。     

小细胞肺癌蛋白质组学研究进展

目的总结蛋白质组学在小细胞肺癌中的研究进展。方法应用PubMed、EMBASE及CNKI期刊数据库检索系统,以＂肺癌,小细胞肺癌、蛋白质组学和研究进展＂等为关键词,检索1995-01-2013-12的相关文献,共检索到英文文献556条,中文文献317条。纳入标准：1）小细胞肺癌;2）蛋白质组学研究;3）蛋白质组学技术。剔除标准：非小细胞肺癌。最后符合分析的文献24篇。结果目前蛋白质组学在小细胞肺癌中的研究主要集中于细胞、组织和血清三个方面,并且已发现多种不同的候选肿瘤标志。结论蛋白质组学研究已广泛深入到小细胞肺癌发病机制、临床早期诊断和治疗等各个方面,为发现小细胞肺癌诊断、治疗及预后判断的潜在生物标志提供了新的思路。     

肿瘤蛋白质组学:过去、现在和将来

将蛋白质组学的技术方法应用到肿瘤生物学的研究中,产生了-门新学科--肿瘤蛋白质组学.它以寻找肿瘤标志物为目的,以蛋白质组学方法为手段,结合肿瘤分子机制的基础研究与肿瘤检测、诊断等临床研究.最终产出能应用于临床的肿瘤检测和治疗的蛋白质靶标.肿瘤蛋白质组学经历了表达谱、修饰谱到活性谱的进化过程,在不同的层面上揭示肿瘤可能的致病机制.本文概述了近年来在常见的恶性肿瘤中进行的肿瘤蛋白质组研究,应用各种蛋白质组技术方法,如二维凝胶电泳(two-dimensional gel eleetrophresis,2DE)、细胞培养稳定同位素标记技术(stable isotope labeling by amino acid in cell culture,SILAC)、基质辅助激光解析(matrix assisted laser desorption/ionization,MALDI)质谱等,找到了大量的蛋白质标志物.将来的挑战在于如何从理论上应用候选标志物解析肿瘤的分子机制,以及从实践上鉴定能真正应用于临床的标志物.     

Perspectives of proteomics in acute myeloid leukemia

Acute myeloid leukemia (AML) is a frequent hematological malignancy. Despite enormous therapeutic efforts that range from various cytotoxic agents to allogeneic stem cell transplantation, overall survival of patients with AML remains unsatisfying. The poor survival rates are mainly due to therapy-related mortality, failure of induction chemotherapy and early relapses. Therefore, novel therapeutic agents that are more efficient and better tolerated are eagerly sought after. For existing therapeutic strategies, there is a lack of markers that are capable of reliably predicting prognosis or the therapeutic response prior to treatment. There is hope that elucidation of the AML-specific proteome will prompt the discovery of novel therapeutic targets and biomarkers in AML. Modern mass-spectrometry instrumentation has acheived excellent performance in terms of sensitivity, resolution and mass accuracy; however, so far, the contribution of proteomics to the care of patients with AML is virtually zero. This might be partly because mass spectrometry instrumentation and protein fractionation still lack true high-throughput capabilities with highest levels of reproducibility, thus hampering large-scale translational studies with clinical samples. Since mass-spectrometry instruments are very intricate devices, their successful operation will hinge on the willingness and ability of mass-spectrometry experts and clinical researchers to adopt new views, learn from each other and cooperate in order to ultimately benefit the patient suffering from AML. This review highlights some clinical problems circumventing the treatment of patients with AML. Furthermore, it provides a brief overview of the technical background of standard proteomics approaches and describes opportunities, challenges and pitfalls of proteomic studies with regards to AML.